Vasculitis

TOPLINE:

Rituximab and cyclophosphamide are equally effective in achieving remission or low disease activity rates in childhood-onset antineutrophil cytoplasmic antibody–associated vasculitis (AAV), and those who received rituximab required a significantly lower steroid dose than those who received cyclophosphamide or a combination therapy.

METHODOLOGY:

• Researchers evaluated the efficacy of rituximab, cyclophosphamide, or a combination of both in pediatric patients diagnosed with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis.
• A total of 104 patients (median age at diagnosis, 14 years; 67% girls) were included from A Registry of Childhood Vasculitis; the majority had a diagnosis of GPA (81%) and renal involvement (87%). Overall, induction therapy involved rituximab for 43%, cyclophosphamide for 46%, and a combination of both for 11% patients.
• The primary endpoint was the rate of achieving remission (Pediatric Vasculitis Activity Score [PVAS] of 0) or low disease activity (PVAS ≤ 2) at the post-induction visit (4-6 months after diagnosis).
• The secondary endpoints were the degree of disease-related damage at 12- and 24-month visits and rates of drug-related hospitalization occurring between the diagnosis and post-induction visits.

TAKEAWAY:

• At the post-induction visit, 63% patients achieved remission or low disease activity, with the rates being similar between patients who received rituximab and those who received cyclophosphamide (64% vs 62%).
• Patients treated with rituximab required a significantly lower median steroid dose (0.13 mg/kg per day) than those treated with cyclophosphamide (0.3 mg/kg per day) or the combination therapy (0.3 mg/kg per day; P < .001) at the post-induction visit.
• Overall, 61% and 56% patients receiving rituximab and cyclophosphamide, respectively, had disease-related damage measure on the Pediatric Vasculitis Damage Index at the 12-month visit; however, the degree of damage was low.
• The percentage of patients requiring hospitalization was higher in the rituximab group than in the cyclophosphamide group (22% vs 10%), primarily stemming from drug- or infection-related causes (11% vs 2%).

IN PRACTICE:

“The results of this study may assist with current clinical decision-making with regard to the choice of induction medications in childhood-onset AAV and will complement the ongoing [Childhood Arthritis and Rheumatology Research Alliance] prospective [consensus treatment plans] study,” the authors wrote.

SOURCE:

This study was led by Samuel J. Gagne, MD, Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center in Pennsylvania, and was published online in Arthritis Care & Research.

LIMITATIONS:

Study limitations included the inconsistencies in glucocorticoid dosing, which may have affected remission rates. Moreover, data on the adverse events not requiring hospitalization and long-term adverse events were not captured.

DISCLOSURES:

This study received funding through a Nationwide Children’s Hospital intramural grant award. The authors reported no potential 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 first appeared on Medscape.com.

TOPLINE:

Rituximab and cyclophosphamide are equally effective in achieving remission or low disease activity rates in childhood-onset antineutrophil cytoplasmic antibody–associated vasculitis (AAV), and those who received rituximab required a significantly lower steroid dose than those who received cyclophosphamide or a combination therapy.

METHODOLOGY:

• Researchers evaluated the efficacy of rituximab, cyclophosphamide, or a combination of both in pediatric patients diagnosed with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis.
• A total of 104 patients (median age at diagnosis, 14 years; 67% girls) were included from A Registry of Childhood Vasculitis; the majority had a diagnosis of GPA (81%) and renal involvement (87%). Overall, induction therapy involved rituximab for 43%, cyclophosphamide for 46%, and a combination of both for 11% patients.
• The primary endpoint was the rate of achieving remission (Pediatric Vasculitis Activity Score [PVAS] of 0) or low disease activity (PVAS ≤ 2) at the post-induction visit (4-6 months after diagnosis).
• The secondary endpoints were the degree of disease-related damage at 12- and 24-month visits and rates of drug-related hospitalization occurring between the diagnosis and post-induction visits.

TAKEAWAY:

• At the post-induction visit, 63% patients achieved remission or low disease activity, with the rates being similar between patients who received rituximab and those who received cyclophosphamide (64% vs 62%).
• Patients treated with rituximab required a significantly lower median steroid dose (0.13 mg/kg per day) than those treated with cyclophosphamide (0.3 mg/kg per day) or the combination therapy (0.3 mg/kg per day; P < .001) at the post-induction visit.
• Overall, 61% and 56% patients receiving rituximab and cyclophosphamide, respectively, had disease-related damage measure on the Pediatric Vasculitis Damage Index at the 12-month visit; however, the degree of damage was low.
• The percentage of patients requiring hospitalization was higher in the rituximab group than in the cyclophosphamide group (22% vs 10%), primarily stemming from drug- or infection-related causes (11% vs 2%).

IN PRACTICE:

“The results of this study may assist with current clinical decision-making with regard to the choice of induction medications in childhood-onset AAV and will complement the ongoing [Childhood Arthritis and Rheumatology Research Alliance] prospective [consensus treatment plans] study,” the authors wrote.

SOURCE:

This study was led by Samuel J. Gagne, MD, Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center in Pennsylvania, and was published online in Arthritis Care & Research.

LIMITATIONS:

Study limitations included the inconsistencies in glucocorticoid dosing, which may have affected remission rates. Moreover, data on the adverse events not requiring hospitalization and long-term adverse events were not captured.

DISCLOSURES:

This study received funding through a Nationwide Children’s Hospital intramural grant award. The authors reported no potential 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 first appeared on Medscape.com.

TOPLINE:

Rituximab and cyclophosphamide are equally effective in achieving remission or low disease activity rates in childhood-onset antineutrophil cytoplasmic antibody–associated vasculitis (AAV), and those who received rituximab required a significantly lower steroid dose than those who received cyclophosphamide or a combination therapy.

METHODOLOGY:

• Researchers evaluated the efficacy of rituximab, cyclophosphamide, or a combination of both in pediatric patients diagnosed with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis.
• A total of 104 patients (median age at diagnosis, 14 years; 67% girls) were included from A Registry of Childhood Vasculitis; the majority had a diagnosis of GPA (81%) and renal involvement (87%). Overall, induction therapy involved rituximab for 43%, cyclophosphamide for 46%, and a combination of both for 11% patients.
• The primary endpoint was the rate of achieving remission (Pediatric Vasculitis Activity Score [PVAS] of 0) or low disease activity (PVAS ≤ 2) at the post-induction visit (4-6 months after diagnosis).
• The secondary endpoints were the degree of disease-related damage at 12- and 24-month visits and rates of drug-related hospitalization occurring between the diagnosis and post-induction visits.

TAKEAWAY:

• At the post-induction visit, 63% patients achieved remission or low disease activity, with the rates being similar between patients who received rituximab and those who received cyclophosphamide (64% vs 62%).
• Patients treated with rituximab required a significantly lower median steroid dose (0.13 mg/kg per day) than those treated with cyclophosphamide (0.3 mg/kg per day) or the combination therapy (0.3 mg/kg per day; P < .001) at the post-induction visit.
• Overall, 61% and 56% patients receiving rituximab and cyclophosphamide, respectively, had disease-related damage measure on the Pediatric Vasculitis Damage Index at the 12-month visit; however, the degree of damage was low.
• The percentage of patients requiring hospitalization was higher in the rituximab group than in the cyclophosphamide group (22% vs 10%), primarily stemming from drug- or infection-related causes (11% vs 2%).

IN PRACTICE:

“The results of this study may assist with current clinical decision-making with regard to the choice of induction medications in childhood-onset AAV and will complement the ongoing [Childhood Arthritis and Rheumatology Research Alliance] prospective [consensus treatment plans] study,” the authors wrote.

SOURCE:

This study was led by Samuel J. Gagne, MD, Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center in Pennsylvania, and was published online in Arthritis Care & Research.

LIMITATIONS:

Study limitations included the inconsistencies in glucocorticoid dosing, which may have affected remission rates. Moreover, data on the adverse events not requiring hospitalization and long-term adverse events were not captured.

DISCLOSURES:

This study received funding through a Nationwide Children’s Hospital intramural grant award. The authors reported no potential 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 first appeared on Medscape.com.

TOPLINE:

Both infliximab and adalimumab are safe and effective in achieving remission in patients with severe mucocutaneous Behçet syndrome, with adalimumab demonstrating a quicker response time; both drugs also improve quality of life and disease activity scores.

METHODOLOGY:

• Researchers conducted a phase 3 prospective study to evaluate the efficacy and safety of the anti–tumor necrosis factor–alpha agents infliximab and adalimumab in patients with Behçet syndrome presenting with mucocutaneous manifestations and inadequate response to prior treatments who were recruited from four Italian tertiary referral centers specializing in Behçet syndrome.
• Patients were randomly assigned to receive either 5 mg/kg intravenous infliximab at weeks 0, 2, and 6 and then every 6-8 weeks (n = 22; mean age, 46 years; 32% women) or 40 mg subcutaneous adalimumab every 2 weeks (n = 18; mean age, 48 years; 28% women) for 24 weeks.
• Patients were followed-up for an additional 12 weeks after the treatment period, with regular assessments of disease activity, safety, and adherence to treatment.
• The primary outcome was the time to response of mucocutaneous manifestations over 6 months; the secondary outcomes included relapse rates; quality of life, assessed using the Short-Form Health Survey 36; and disease activity, assessed using the Behçet Disease Current Activity Form.
• The safety and tolerability of the drugs were evaluated as the frequency of treatment-emergent adverse events (AEs) and serious AEs, monitored every 2 weeks.

TAKEAWAY:

• The resolution of mucocutaneous manifestations was achieved significantly more quickly with adalimumab than with infliximab, with a median time to response of 42 vs 152 days (P = .001); the proportion of responders was also higher in the adalimumab group than in the infliximab group (94% vs 64%; P = .023).
• Patients in the infliximab group had a higher risk for nonresponse (adjusted hazard ratio [HR], 3.33; P = .012) and relapse (adjusted HR, 7.57; P = .036) than those in the adalimumab group.
• Both infliximab and adalimumab significantly improved the quality of life in all dimensions (P < .05 for all) and disease activity scores (P < .001 for both) from baseline to the end of the study period, with no significant differences found between the groups.
• Two AEs were reported in the adalimumab group, one of which was serious (myocardial infarction); three nonserious AEs were reported in the infliximab group.

IN PRACTICE:

“ADA [adalimumab] and IFX [infliximab] were generally well tolerated and efficacious in patients with BS [Behçet syndrome] who showed an inadequate response to prior treatments with at least AZA [azathioprine] or CyA [cyclosporine],” the authors wrote. “Although a more detailed treat-to-target profile is yet to be better defined, [the study] results are also crucial in terms of prescriptiveness (currently off label), not only in Italy but also beyond national borders, as the evidence coming from real life still needs to be confirmed by growing data from clinical trials.”

SOURCE:

The study was led by Rosaria Talarico, MD, PhD, University of Pisa in Italy, and was published online in Annals of the Rheumatic Diseases.

LIMITATIONS:

The small sample size and the distinctive study design may have limited the generalizability of the findings.

DISCLOSURES:

This study was funded through a grant from the Italian Medicines Agency. 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 first appeared on Medscape.com.

TOPLINE:

Both infliximab and adalimumab are safe and effective in achieving remission in patients with severe mucocutaneous Behçet syndrome, with adalimumab demonstrating a quicker response time; both drugs also improve quality of life and disease activity scores.

METHODOLOGY:

• Researchers conducted a phase 3 prospective study to evaluate the efficacy and safety of the anti–tumor necrosis factor–alpha agents infliximab and adalimumab in patients with Behçet syndrome presenting with mucocutaneous manifestations and inadequate response to prior treatments who were recruited from four Italian tertiary referral centers specializing in Behçet syndrome.
• Patients were randomly assigned to receive either 5 mg/kg intravenous infliximab at weeks 0, 2, and 6 and then every 6-8 weeks (n = 22; mean age, 46 years; 32% women) or 40 mg subcutaneous adalimumab every 2 weeks (n = 18; mean age, 48 years; 28% women) for 24 weeks.
• Patients were followed-up for an additional 12 weeks after the treatment period, with regular assessments of disease activity, safety, and adherence to treatment.
• The primary outcome was the time to response of mucocutaneous manifestations over 6 months; the secondary outcomes included relapse rates; quality of life, assessed using the Short-Form Health Survey 36; and disease activity, assessed using the Behçet Disease Current Activity Form.
• The safety and tolerability of the drugs were evaluated as the frequency of treatment-emergent adverse events (AEs) and serious AEs, monitored every 2 weeks.

TAKEAWAY:

• The resolution of mucocutaneous manifestations was achieved significantly more quickly with adalimumab than with infliximab, with a median time to response of 42 vs 152 days (P = .001); the proportion of responders was also higher in the adalimumab group than in the infliximab group (94% vs 64%; P = .023).
• Patients in the infliximab group had a higher risk for nonresponse (adjusted hazard ratio [HR], 3.33; P = .012) and relapse (adjusted HR, 7.57; P = .036) than those in the adalimumab group.
• Both infliximab and adalimumab significantly improved the quality of life in all dimensions (P < .05 for all) and disease activity scores (P < .001 for both) from baseline to the end of the study period, with no significant differences found between the groups.
• Two AEs were reported in the adalimumab group, one of which was serious (myocardial infarction); three nonserious AEs were reported in the infliximab group.

IN PRACTICE:

“ADA [adalimumab] and IFX [infliximab] were generally well tolerated and efficacious in patients with BS [Behçet syndrome] who showed an inadequate response to prior treatments with at least AZA [azathioprine] or CyA [cyclosporine],” the authors wrote. “Although a more detailed treat-to-target profile is yet to be better defined, [the study] results are also crucial in terms of prescriptiveness (currently off label), not only in Italy but also beyond national borders, as the evidence coming from real life still needs to be confirmed by growing data from clinical trials.”

SOURCE:

The study was led by Rosaria Talarico, MD, PhD, University of Pisa in Italy, and was published online in Annals of the Rheumatic Diseases.

LIMITATIONS:

The small sample size and the distinctive study design may have limited the generalizability of the findings.

DISCLOSURES:

This study was funded through a grant from the Italian Medicines Agency. 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 first appeared on Medscape.com.

TOPLINE:

Both infliximab and adalimumab are safe and effective in achieving remission in patients with severe mucocutaneous Behçet syndrome, with adalimumab demonstrating a quicker response time; both drugs also improve quality of life and disease activity scores.

METHODOLOGY:

• Researchers conducted a phase 3 prospective study to evaluate the efficacy and safety of the anti–tumor necrosis factor–alpha agents infliximab and adalimumab in patients with Behçet syndrome presenting with mucocutaneous manifestations and inadequate response to prior treatments who were recruited from four Italian tertiary referral centers specializing in Behçet syndrome.
• Patients were randomly assigned to receive either 5 mg/kg intravenous infliximab at weeks 0, 2, and 6 and then every 6-8 weeks (n = 22; mean age, 46 years; 32% women) or 40 mg subcutaneous adalimumab every 2 weeks (n = 18; mean age, 48 years; 28% women) for 24 weeks.
• Patients were followed-up for an additional 12 weeks after the treatment period, with regular assessments of disease activity, safety, and adherence to treatment.
• The primary outcome was the time to response of mucocutaneous manifestations over 6 months; the secondary outcomes included relapse rates; quality of life, assessed using the Short-Form Health Survey 36; and disease activity, assessed using the Behçet Disease Current Activity Form.
• The safety and tolerability of the drugs were evaluated as the frequency of treatment-emergent adverse events (AEs) and serious AEs, monitored every 2 weeks.

TAKEAWAY:

• The resolution of mucocutaneous manifestations was achieved significantly more quickly with adalimumab than with infliximab, with a median time to response of 42 vs 152 days (P = .001); the proportion of responders was also higher in the adalimumab group than in the infliximab group (94% vs 64%; P = .023).
• Patients in the infliximab group had a higher risk for nonresponse (adjusted hazard ratio [HR], 3.33; P = .012) and relapse (adjusted HR, 7.57; P = .036) than those in the adalimumab group.
• Both infliximab and adalimumab significantly improved the quality of life in all dimensions (P < .05 for all) and disease activity scores (P < .001 for both) from baseline to the end of the study period, with no significant differences found between the groups.
• Two AEs were reported in the adalimumab group, one of which was serious (myocardial infarction); three nonserious AEs were reported in the infliximab group.

IN PRACTICE:

“ADA [adalimumab] and IFX [infliximab] were generally well tolerated and efficacious in patients with BS [Behçet syndrome] who showed an inadequate response to prior treatments with at least AZA [azathioprine] or CyA [cyclosporine],” the authors wrote. “Although a more detailed treat-to-target profile is yet to be better defined, [the study] results are also crucial in terms of prescriptiveness (currently off label), not only in Italy but also beyond national borders, as the evidence coming from real life still needs to be confirmed by growing data from clinical trials.”

SOURCE:

The study was led by Rosaria Talarico, MD, PhD, University of Pisa in Italy, and was published online in Annals of the Rheumatic Diseases.

LIMITATIONS:

The small sample size and the distinctive study design may have limited the generalizability of the findings.

DISCLOSURES:

This study was funded through a grant from the Italian Medicines Agency. 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 first appeared on Medscape.com.

TOPLINE: 

In patients with giant cell arteritis (GCA), intravenous methylprednisolone compared with oral glucocorticoids alone does not improve visual acuity and increases the risk for diabetes within the first year. Survival rates do not differ with these two treatments.

METHODOLOGY:

• Researchers conducted a population-based retrospective study at three centers in Sweden to assess the clinical characteristics, treatment-related toxicity, and mortality in patients with GCA who were receiving high-dose intravenous methylprednisolone.
• A total of 419 patients with biopsy-confirmed GCA (mean age at diagnosis, 75 years; 69% women) diagnosed from 2004 to 2019 were included.
• Patients were treated with either intravenous methylprednisolone (n = 111) at a dose of 500-1000 mg per day for 3 consecutive days or oral glucocorticoids alone (n = 308).
• Ischemic visual complications considered to indicate visual involvement were confirmed by an ophthalmologist, and data on visual acuity were collected from ophthalmologic clinic records at initial consultations and follow-up at 3-18 months.

TAKEAWAY:

• Despite a tendency toward improvement, no significant difference in visual acuity was observed with intravenous methylprednisolone compared with oral glucocorticoids.
• Patients treated with intravenous methylprednisolone had a higher risk for newly diagnosed diabetes within a year of GCA diagnosis (odds ratio [OR], 2.59; P = .01).
• The risk for diabetes remained elevated even after adjustment for the cumulative oral glucocorticoid dose at 3 months (adjusted OR, 3.30; P = .01).
• Survival rates did not significantly differ between the treatment groups over a mean follow-up of 6.6 years.

IN PRACTICE:

“In this study on the use of intravenous methylprednisolone treatment in GCA, we found no evidence of a beneficial effect in improving visual acuity or enabling more rapid tapering of the oral glucocorticoid dose,” the authors wrote. “The use of IVMP [intravenous methylprednisolone] was associated with an increased risk of diabetes during the first year compared with oral GC [glucocorticoid], raising questions about the value of IVMP in GCA treatment.”

SOURCE:

The study, led by Hampus Henningson, Department of Clinical Sciences, Rheumatology, Lund University, Lund, Sweden, was published online in Rheumatology.

LIMITATIONS: 

The retrospective nature of the study may have resulted in missing data and difficulty in accurately quantifying the cumulative glucocorticoid doses. The study did not validate the diagnoses of comorbidities but relied solely on diagnostic codes.

DISCLOSURES:

This study was supported by the Swedish Research Council, Swedish Rheumatism Association, Swedish Medical Society, Alfred Österlund’s Foundation, and King Gustaf V’s 80-year foundation. 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 first appeared on Medscape.com.

TOPLINE: 

In patients with giant cell arteritis (GCA), intravenous methylprednisolone compared with oral glucocorticoids alone does not improve visual acuity and increases the risk for diabetes within the first year. Survival rates do not differ with these two treatments.

METHODOLOGY:

• Researchers conducted a population-based retrospective study at three centers in Sweden to assess the clinical characteristics, treatment-related toxicity, and mortality in patients with GCA who were receiving high-dose intravenous methylprednisolone.
• A total of 419 patients with biopsy-confirmed GCA (mean age at diagnosis, 75 years; 69% women) diagnosed from 2004 to 2019 were included.
• Patients were treated with either intravenous methylprednisolone (n = 111) at a dose of 500-1000 mg per day for 3 consecutive days or oral glucocorticoids alone (n = 308).
• Ischemic visual complications considered to indicate visual involvement were confirmed by an ophthalmologist, and data on visual acuity were collected from ophthalmologic clinic records at initial consultations and follow-up at 3-18 months.

TAKEAWAY:

• Despite a tendency toward improvement, no significant difference in visual acuity was observed with intravenous methylprednisolone compared with oral glucocorticoids.
• Patients treated with intravenous methylprednisolone had a higher risk for newly diagnosed diabetes within a year of GCA diagnosis (odds ratio [OR], 2.59; P = .01).
• The risk for diabetes remained elevated even after adjustment for the cumulative oral glucocorticoid dose at 3 months (adjusted OR, 3.30; P = .01).
• Survival rates did not significantly differ between the treatment groups over a mean follow-up of 6.6 years.

IN PRACTICE:

“In this study on the use of intravenous methylprednisolone treatment in GCA, we found no evidence of a beneficial effect in improving visual acuity or enabling more rapid tapering of the oral glucocorticoid dose,” the authors wrote. “The use of IVMP [intravenous methylprednisolone] was associated with an increased risk of diabetes during the first year compared with oral GC [glucocorticoid], raising questions about the value of IVMP in GCA treatment.”

SOURCE:

The study, led by Hampus Henningson, Department of Clinical Sciences, Rheumatology, Lund University, Lund, Sweden, was published online in Rheumatology.

LIMITATIONS: 

The retrospective nature of the study may have resulted in missing data and difficulty in accurately quantifying the cumulative glucocorticoid doses. The study did not validate the diagnoses of comorbidities but relied solely on diagnostic codes.

DISCLOSURES:

This study was supported by the Swedish Research Council, Swedish Rheumatism Association, Swedish Medical Society, Alfred Österlund’s Foundation, and King Gustaf V’s 80-year foundation. 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 first appeared on Medscape.com.

TOPLINE: 

In patients with giant cell arteritis (GCA), intravenous methylprednisolone compared with oral glucocorticoids alone does not improve visual acuity and increases the risk for diabetes within the first year. Survival rates do not differ with these two treatments.

METHODOLOGY:

• Researchers conducted a population-based retrospective study at three centers in Sweden to assess the clinical characteristics, treatment-related toxicity, and mortality in patients with GCA who were receiving high-dose intravenous methylprednisolone.
• A total of 419 patients with biopsy-confirmed GCA (mean age at diagnosis, 75 years; 69% women) diagnosed from 2004 to 2019 were included.
• Patients were treated with either intravenous methylprednisolone (n = 111) at a dose of 500-1000 mg per day for 3 consecutive days or oral glucocorticoids alone (n = 308).
• Ischemic visual complications considered to indicate visual involvement were confirmed by an ophthalmologist, and data on visual acuity were collected from ophthalmologic clinic records at initial consultations and follow-up at 3-18 months.

TAKEAWAY:

• Despite a tendency toward improvement, no significant difference in visual acuity was observed with intravenous methylprednisolone compared with oral glucocorticoids.
• Patients treated with intravenous methylprednisolone had a higher risk for newly diagnosed diabetes within a year of GCA diagnosis (odds ratio [OR], 2.59; P = .01).
• The risk for diabetes remained elevated even after adjustment for the cumulative oral glucocorticoid dose at 3 months (adjusted OR, 3.30; P = .01).
• Survival rates did not significantly differ between the treatment groups over a mean follow-up of 6.6 years.

IN PRACTICE:

“In this study on the use of intravenous methylprednisolone treatment in GCA, we found no evidence of a beneficial effect in improving visual acuity or enabling more rapid tapering of the oral glucocorticoid dose,” the authors wrote. “The use of IVMP [intravenous methylprednisolone] was associated with an increased risk of diabetes during the first year compared with oral GC [glucocorticoid], raising questions about the value of IVMP in GCA treatment.”

SOURCE:

The study, led by Hampus Henningson, Department of Clinical Sciences, Rheumatology, Lund University, Lund, Sweden, was published online in Rheumatology.

LIMITATIONS: 

The retrospective nature of the study may have resulted in missing data and difficulty in accurately quantifying the cumulative glucocorticoid doses. The study did not validate the diagnoses of comorbidities but relied solely on diagnostic codes.

DISCLOSURES:

This study was supported by the Swedish Research Council, Swedish Rheumatism Association, Swedish Medical Society, Alfred Österlund’s Foundation, and King Gustaf V’s 80-year foundation. 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 first appeared on Medscape.com.

TOPLINE:

Older adults with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis face a higher risk for end-stage renal disease or mortality and severe infections. However, frailty, more than age, predicts severe infections within 2 years of diagnosis.

METHODOLOGY:

• Researchers conducted a retrospective cohort study using data from the Mass General Brigham ANCA-associated vasculitis cohort in the United States.
• They included 234 individuals (median age, 75 years) with incident ANCA-associated vasculitis who were treated from January 2002 to December 2019.
• Baseline frailty was measured using a claims-based frailty index, with data collected in the year before treatment initiation; individuals were categorized as those who were nonfrail, prefrail, mildly frail, and moderately to severely frail.
• Frailty, either mild or moderate to severe, was noted in 44 of 118 individuals aged ≥ 75 years and in 25 of 116 individuals aged 65-74 years.
• The outcomes of interest were the incidences of end-stage renal disease or death and severe infections within 2 years of diagnosis. The association of age and frailty with clinical outcomes was assessed in those aged 65-74 years and ≥ 75 years.

TAKEAWAY:

• Frailty was a significant predictor of severe infections within 2 years of ANCA-associated vasculitis diagnosis (adjusted hazard ratio [aHR], 8.46; 95% CI, 3.95-18.14), showing a stronger association than seen for chronological age ≥ 75 years (aHR, 2.52; 95% CI, 1.26-5.04).
• The incidence of severe infections was higher in those with vs without frailty in the age groups 65-74 years (38.9 vs 0.8 cases per 100 person-years) and ≥ 75 years (61.9 vs 12.3 cases per 100 person-years).
• Older age (≥ 75 years) was associated with an increased risk for end-stage renal disease or death (aHR, 4.50; 95% CI, 1.83-11.09); however, frailty was not.
• The effect of frailty on end-stage renal disease or death varied by age, with a larger difference observed in individuals aged 65-74 years (frail vs nonfrail, 7.5 vs 2.0 cases per 100 person-years) than in those aged ≥ 75 years (13.5 vs 16.0 cases per 100 person-years).

IN PRACTICE:

“Our results highlight the fact that assessment of frailty in the care of older adults with ANCA-associated vasculitis can distinguish a group of patients at increased risk of severe infections who might benefit from interventions to minimize infection risk and optimize outcomes,” the authors wrote.

“Incorporating frailty screening into the management of ANCA-associated vasculitis provides an opportunity to offer personalized, evidence-based care to frail older adults,” Alexandra Legge, MD, Dalhousie University, Halifax, Nova Scotia, Canada, wrote in an associated comment published online in The Lancet Rheumatology.
 

SOURCE:

This study was led by Sebastian E. Sattui, MD, Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh in Pennsylvania. It was published online on September 18, 2024, in The Lancet Rheumatology.

LIMITATIONS:

The study’s observational design and single-center setting limited the generalizability of the findings. Residual confounding may have been possible despite adjustments for relevant baseline factors. The requirement of at least one healthcare encounter before baseline may have underrepresented individuals without frailty. Differences in treatment patterns after the baseline period were not controlled for.

DISCLOSURES:

The study was supported by the National Institutes of Health and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Some authors reported receiving grants, research support, consulting fees, honoraria, or royalties or serving on advisory boards of pharmaceutical companies and other sources outside of 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:

Older adults with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis face a higher risk for end-stage renal disease or mortality and severe infections. However, frailty, more than age, predicts severe infections within 2 years of diagnosis.

METHODOLOGY:

• Researchers conducted a retrospective cohort study using data from the Mass General Brigham ANCA-associated vasculitis cohort in the United States.
• They included 234 individuals (median age, 75 years) with incident ANCA-associated vasculitis who were treated from January 2002 to December 2019.
• Baseline frailty was measured using a claims-based frailty index, with data collected in the year before treatment initiation; individuals were categorized as those who were nonfrail, prefrail, mildly frail, and moderately to severely frail.
• Frailty, either mild or moderate to severe, was noted in 44 of 118 individuals aged ≥ 75 years and in 25 of 116 individuals aged 65-74 years.
• The outcomes of interest were the incidences of end-stage renal disease or death and severe infections within 2 years of diagnosis. The association of age and frailty with clinical outcomes was assessed in those aged 65-74 years and ≥ 75 years.

TAKEAWAY:

• Frailty was a significant predictor of severe infections within 2 years of ANCA-associated vasculitis diagnosis (adjusted hazard ratio [aHR], 8.46; 95% CI, 3.95-18.14), showing a stronger association than seen for chronological age ≥ 75 years (aHR, 2.52; 95% CI, 1.26-5.04).
• The incidence of severe infections was higher in those with vs without frailty in the age groups 65-74 years (38.9 vs 0.8 cases per 100 person-years) and ≥ 75 years (61.9 vs 12.3 cases per 100 person-years).
• Older age (≥ 75 years) was associated with an increased risk for end-stage renal disease or death (aHR, 4.50; 95% CI, 1.83-11.09); however, frailty was not.
• The effect of frailty on end-stage renal disease or death varied by age, with a larger difference observed in individuals aged 65-74 years (frail vs nonfrail, 7.5 vs 2.0 cases per 100 person-years) than in those aged ≥ 75 years (13.5 vs 16.0 cases per 100 person-years).

IN PRACTICE:

“Our results highlight the fact that assessment of frailty in the care of older adults with ANCA-associated vasculitis can distinguish a group of patients at increased risk of severe infections who might benefit from interventions to minimize infection risk and optimize outcomes,” the authors wrote.

“Incorporating frailty screening into the management of ANCA-associated vasculitis provides an opportunity to offer personalized, evidence-based care to frail older adults,” Alexandra Legge, MD, Dalhousie University, Halifax, Nova Scotia, Canada, wrote in an associated comment published online in The Lancet Rheumatology.
 

SOURCE:

This study was led by Sebastian E. Sattui, MD, Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh in Pennsylvania. It was published online on September 18, 2024, in The Lancet Rheumatology.

LIMITATIONS:

The study’s observational design and single-center setting limited the generalizability of the findings. Residual confounding may have been possible despite adjustments for relevant baseline factors. The requirement of at least one healthcare encounter before baseline may have underrepresented individuals without frailty. Differences in treatment patterns after the baseline period were not controlled for.

DISCLOSURES:

The study was supported by the National Institutes of Health and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Some authors reported receiving grants, research support, consulting fees, honoraria, or royalties or serving on advisory boards of pharmaceutical companies and other sources outside of 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:

Older adults with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis face a higher risk for end-stage renal disease or mortality and severe infections. However, frailty, more than age, predicts severe infections within 2 years of diagnosis.

METHODOLOGY:

• Researchers conducted a retrospective cohort study using data from the Mass General Brigham ANCA-associated vasculitis cohort in the United States.
• They included 234 individuals (median age, 75 years) with incident ANCA-associated vasculitis who were treated from January 2002 to December 2019.
• Baseline frailty was measured using a claims-based frailty index, with data collected in the year before treatment initiation; individuals were categorized as those who were nonfrail, prefrail, mildly frail, and moderately to severely frail.
• Frailty, either mild or moderate to severe, was noted in 44 of 118 individuals aged ≥ 75 years and in 25 of 116 individuals aged 65-74 years.
• The outcomes of interest were the incidences of end-stage renal disease or death and severe infections within 2 years of diagnosis. The association of age and frailty with clinical outcomes was assessed in those aged 65-74 years and ≥ 75 years.

TAKEAWAY:

• Frailty was a significant predictor of severe infections within 2 years of ANCA-associated vasculitis diagnosis (adjusted hazard ratio [aHR], 8.46; 95% CI, 3.95-18.14), showing a stronger association than seen for chronological age ≥ 75 years (aHR, 2.52; 95% CI, 1.26-5.04).
• The incidence of severe infections was higher in those with vs without frailty in the age groups 65-74 years (38.9 vs 0.8 cases per 100 person-years) and ≥ 75 years (61.9 vs 12.3 cases per 100 person-years).
• Older age (≥ 75 years) was associated with an increased risk for end-stage renal disease or death (aHR, 4.50; 95% CI, 1.83-11.09); however, frailty was not.
• The effect of frailty on end-stage renal disease or death varied by age, with a larger difference observed in individuals aged 65-74 years (frail vs nonfrail, 7.5 vs 2.0 cases per 100 person-years) than in those aged ≥ 75 years (13.5 vs 16.0 cases per 100 person-years).

IN PRACTICE:

“Our results highlight the fact that assessment of frailty in the care of older adults with ANCA-associated vasculitis can distinguish a group of patients at increased risk of severe infections who might benefit from interventions to minimize infection risk and optimize outcomes,” the authors wrote.

“Incorporating frailty screening into the management of ANCA-associated vasculitis provides an opportunity to offer personalized, evidence-based care to frail older adults,” Alexandra Legge, MD, Dalhousie University, Halifax, Nova Scotia, Canada, wrote in an associated comment published online in The Lancet Rheumatology.
 

SOURCE:

This study was led by Sebastian E. Sattui, MD, Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh in Pennsylvania. It was published online on September 18, 2024, in The Lancet Rheumatology.

LIMITATIONS:

The study’s observational design and single-center setting limited the generalizability of the findings. Residual confounding may have been possible despite adjustments for relevant baseline factors. The requirement of at least one healthcare encounter before baseline may have underrepresented individuals without frailty. Differences in treatment patterns after the baseline period were not controlled for.

DISCLOSURES:

The study was supported by the National Institutes of Health and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Some authors reported receiving grants, research support, consulting fees, honoraria, or royalties or serving on advisory boards of pharmaceutical companies and other sources outside of 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.

The Food and Drug Administration (FDA) has approved benralizumab (Fasenra) for the treatment of adults with eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss syndrome.

The drug is the second approved biologic for the treatment of EGPA. The first, mepolizumab (Nucala), was approved in 2017.

“This disease has a devastating impact on patients and the quality of their life, and they need more treatment options. The approval of another treatment in EGPA is welcome news to the approximately 15,000 patients living in the US with this difficult-to-treat rare disease,” said Joyce Kullman, executive director of the Vasculitis Foundation, in a press release on September 18. 

Benralizumab, developed by AstraZeneca, is a monoclonal antibody against the interleukin-5 alpha receptor expressed on eosinophils. The drug was first approved in 2017 as an add-on treatment for patients 12 years and older with severe eosinophilic asthma, and is now approved for use in children aged 6 years and older. 

The new indication was based on positive results from a noninferiority trial comparing benralizumab and mepolizumab. For the trial, published in the New England Journal of Medicine earlier in 2024, 140 adults with relapsing or refractory EGPA were randomized to a 30-mg subcutaneous injection of benralizumab or three separate 100-mg mepolizumab injections every 4 weeks for 1 year. At weeks 36 and 48, 59% of patients in the benralizumab group and 56% of patients in the mepolizumab group achieved remission (95% CI, –13 to 18; P = .73 for superiority). From week 42 to 52, 41% of patients who received benralizumab completely stopped taking oral glucocorticoids, compared with 26% of those who received mepolizumab.

“Patients often rely on long-term oral corticosteroids, which can cause serious and lasting side effects. Benralizumab is a much-needed treatment option, with data showing that not only is remission an achievable goal for EGPA patients, but benralizumab can also help patients taper off steroid therapy,” Michael Wechsler, MD, director of The Asthma Institute at National Jewish Health in Denver, Colorado, and the international coordinating investigator for the clinical trial, said in the press release.

Benralizumab is administered via subcutaneous injection. In adults with EGPA, the recommended dosage is 30 mg every 4 weeks for the first three doses, then once every 8 weeks.

The most common adverse reactions include headache and pharyngitis, according to the prescribing information. 

Benralizumab is also in development for the treatment of chronic obstructive pulmonary disease, chronic rhinosinusitis with nasal polyps, and hypereosinophilic syndrome.

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

The Food and Drug Administration (FDA) has approved benralizumab (Fasenra) for the treatment of adults with eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss syndrome.

The drug is the second approved biologic for the treatment of EGPA. The first, mepolizumab (Nucala), was approved in 2017.

“This disease has a devastating impact on patients and the quality of their life, and they need more treatment options. The approval of another treatment in EGPA is welcome news to the approximately 15,000 patients living in the US with this difficult-to-treat rare disease,” said Joyce Kullman, executive director of the Vasculitis Foundation, in a press release on September 18. 

Benralizumab, developed by AstraZeneca, is a monoclonal antibody against the interleukin-5 alpha receptor expressed on eosinophils. The drug was first approved in 2017 as an add-on treatment for patients 12 years and older with severe eosinophilic asthma, and is now approved for use in children aged 6 years and older. 

The new indication was based on positive results from a noninferiority trial comparing benralizumab and mepolizumab. For the trial, published in the New England Journal of Medicine earlier in 2024, 140 adults with relapsing or refractory EGPA were randomized to a 30-mg subcutaneous injection of benralizumab or three separate 100-mg mepolizumab injections every 4 weeks for 1 year. At weeks 36 and 48, 59% of patients in the benralizumab group and 56% of patients in the mepolizumab group achieved remission (95% CI, –13 to 18; P = .73 for superiority). From week 42 to 52, 41% of patients who received benralizumab completely stopped taking oral glucocorticoids, compared with 26% of those who received mepolizumab.

“Patients often rely on long-term oral corticosteroids, which can cause serious and lasting side effects. Benralizumab is a much-needed treatment option, with data showing that not only is remission an achievable goal for EGPA patients, but benralizumab can also help patients taper off steroid therapy,” Michael Wechsler, MD, director of The Asthma Institute at National Jewish Health in Denver, Colorado, and the international coordinating investigator for the clinical trial, said in the press release.

Benralizumab is administered via subcutaneous injection. In adults with EGPA, the recommended dosage is 30 mg every 4 weeks for the first three doses, then once every 8 weeks.

The most common adverse reactions include headache and pharyngitis, according to the prescribing information. 

Benralizumab is also in development for the treatment of chronic obstructive pulmonary disease, chronic rhinosinusitis with nasal polyps, and hypereosinophilic syndrome.

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

The Food and Drug Administration (FDA) has approved benralizumab (Fasenra) for the treatment of adults with eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss syndrome.

The drug is the second approved biologic for the treatment of EGPA. The first, mepolizumab (Nucala), was approved in 2017.

“This disease has a devastating impact on patients and the quality of their life, and they need more treatment options. The approval of another treatment in EGPA is welcome news to the approximately 15,000 patients living in the US with this difficult-to-treat rare disease,” said Joyce Kullman, executive director of the Vasculitis Foundation, in a press release on September 18. 

Benralizumab, developed by AstraZeneca, is a monoclonal antibody against the interleukin-5 alpha receptor expressed on eosinophils. The drug was first approved in 2017 as an add-on treatment for patients 12 years and older with severe eosinophilic asthma, and is now approved for use in children aged 6 years and older. 

The new indication was based on positive results from a noninferiority trial comparing benralizumab and mepolizumab. For the trial, published in the New England Journal of Medicine earlier in 2024, 140 adults with relapsing or refractory EGPA were randomized to a 30-mg subcutaneous injection of benralizumab or three separate 100-mg mepolizumab injections every 4 weeks for 1 year. At weeks 36 and 48, 59% of patients in the benralizumab group and 56% of patients in the mepolizumab group achieved remission (95% CI, –13 to 18; P = .73 for superiority). From week 42 to 52, 41% of patients who received benralizumab completely stopped taking oral glucocorticoids, compared with 26% of those who received mepolizumab.

“Patients often rely on long-term oral corticosteroids, which can cause serious and lasting side effects. Benralizumab is a much-needed treatment option, with data showing that not only is remission an achievable goal for EGPA patients, but benralizumab can also help patients taper off steroid therapy,” Michael Wechsler, MD, director of The Asthma Institute at National Jewish Health in Denver, Colorado, and the international coordinating investigator for the clinical trial, said in the press release.

Benralizumab is administered via subcutaneous injection. In adults with EGPA, the recommended dosage is 30 mg every 4 weeks for the first three doses, then once every 8 weeks.

The most common adverse reactions include headache and pharyngitis, according to the prescribing information. 

Benralizumab is also in development for the treatment of chronic obstructive pulmonary disease, chronic rhinosinusitis with nasal polyps, and hypereosinophilic syndrome.

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

TOPLINE:

A data-driven subclassification of antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis has identified five distinct clusters with varying degrees of kidney involvement and systemic inflammation, offering insights into improved patient stratification and treatment approaches.

METHODOLOGY:

• ANCA-associated vasculitis is a rare and complex autoimmune disease that is traditionally classified into granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA).
• Researchers employed advanced artificial intelligence and big data techniques to identify phenotypically distinct subgroups of ANCA-associated vasculitis and developed a classification system using real-world patient data from the Federated Vasculitis Registry consortium.
• They included 3868 patients diagnosed with ANCA-associated vasculitis between November 1, 1966, and March 1, 2023 (mean age at diagnosis, 57.2 years; 51.9% men), across six European vasculitis registries; while a majority of patients (62.9%) were diagnosed with GPA, the remaining 37.1% were diagnosed with MPA.
• Overall, 17 clinical and demographic variables such as the age at diagnosis, gender, serum creatinine and C-reactive protein levels, the type of ANCA, and the involvement of various organ systems were used to create a model for categorizing patients into different clusters.
• The median follow-up duration was 4.2 years.

TAKEAWAY:

• Five distinct clusters were identified in ANCA-associated vasculitis; three had significant kidney involvement (the severe kidney cluster, myeloperoxidase-ANCA-positive kidney cluster, and proteinase 3-ANCA-positive kidney cluster) and two had minimal kidney involvement (young respiratory cluster and inflammatory multisystem cluster).
• The clusters with significant kidney involvement were associated with poorer outcomes, including a higher risk for kidney failure and death. The severe kidney cluster had the poorest prognosis, with mortality and the rate of end-stage kidney failure being 30.5% and 41.6%, respectively.
• The young respiratory cluster, characterized by predominant ear-nose-throat involvement and low systemic inflammation, showed the best prognostic outcomes.
• This cluster membership model showed a greater predictive accuracy for patient and kidney survival than traditional methods based on clinical diagnosis or ANCA specificity.

IN PRACTICE:

“These findings highlight the necessity of recognizing severe kidney disease at the time of diagnosis as an indicator of poor outcome, thereby necessitating intensified treatment approaches,” experts from the Department of Internal Medicine IV (Nephrology and Hypertension), Medical University of Innsbruck, Austria, wrote in an accompanying editorial published online on August 22, 2024, in The Lancet Rheumatology.

SOURCE:

This study was led by Karl Gisslander, Department of Clinical Sciences, Lund University, Lund, Sweden, and was published online on August 22, 2024, in The Lancet Rheumatology.

LIMITATIONS:

Data on estimated glomerular filtration rate recovery in clusters with kidney disease were lacking. Populations from East Asia, where myeloperoxidase-ANCA positivity is more prevalent, were not included.

DISCLOSURES:

This study received funding from the European Union’s Horizon 2020 research and innovation program under the European Joint Programme on Rare Diseases. Some authors declared serving on advisory boards or receiving grants, contracts, travel support, consulting fees, payments, or honoraria from various pharmaceutical companies and other institutions.

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 data-driven subclassification of antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis has identified five distinct clusters with varying degrees of kidney involvement and systemic inflammation, offering insights into improved patient stratification and treatment approaches.

METHODOLOGY:

• ANCA-associated vasculitis is a rare and complex autoimmune disease that is traditionally classified into granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA).
• Researchers employed advanced artificial intelligence and big data techniques to identify phenotypically distinct subgroups of ANCA-associated vasculitis and developed a classification system using real-world patient data from the Federated Vasculitis Registry consortium.
• They included 3868 patients diagnosed with ANCA-associated vasculitis between November 1, 1966, and March 1, 2023 (mean age at diagnosis, 57.2 years; 51.9% men), across six European vasculitis registries; while a majority of patients (62.9%) were diagnosed with GPA, the remaining 37.1% were diagnosed with MPA.
• Overall, 17 clinical and demographic variables such as the age at diagnosis, gender, serum creatinine and C-reactive protein levels, the type of ANCA, and the involvement of various organ systems were used to create a model for categorizing patients into different clusters.
• The median follow-up duration was 4.2 years.

TAKEAWAY:

• Five distinct clusters were identified in ANCA-associated vasculitis; three had significant kidney involvement (the severe kidney cluster, myeloperoxidase-ANCA-positive kidney cluster, and proteinase 3-ANCA-positive kidney cluster) and two had minimal kidney involvement (young respiratory cluster and inflammatory multisystem cluster).
• The clusters with significant kidney involvement were associated with poorer outcomes, including a higher risk for kidney failure and death. The severe kidney cluster had the poorest prognosis, with mortality and the rate of end-stage kidney failure being 30.5% and 41.6%, respectively.
• The young respiratory cluster, characterized by predominant ear-nose-throat involvement and low systemic inflammation, showed the best prognostic outcomes.
• This cluster membership model showed a greater predictive accuracy for patient and kidney survival than traditional methods based on clinical diagnosis or ANCA specificity.

IN PRACTICE:

“These findings highlight the necessity of recognizing severe kidney disease at the time of diagnosis as an indicator of poor outcome, thereby necessitating intensified treatment approaches,” experts from the Department of Internal Medicine IV (Nephrology and Hypertension), Medical University of Innsbruck, Austria, wrote in an accompanying editorial published online on August 22, 2024, in The Lancet Rheumatology.

SOURCE:

This study was led by Karl Gisslander, Department of Clinical Sciences, Lund University, Lund, Sweden, and was published online on August 22, 2024, in The Lancet Rheumatology.

LIMITATIONS:

Data on estimated glomerular filtration rate recovery in clusters with kidney disease were lacking. Populations from East Asia, where myeloperoxidase-ANCA positivity is more prevalent, were not included.

DISCLOSURES:

This study received funding from the European Union’s Horizon 2020 research and innovation program under the European Joint Programme on Rare Diseases. Some authors declared serving on advisory boards or receiving grants, contracts, travel support, consulting fees, payments, or honoraria from various pharmaceutical companies and other institutions.

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 data-driven subclassification of antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis has identified five distinct clusters with varying degrees of kidney involvement and systemic inflammation, offering insights into improved patient stratification and treatment approaches.

METHODOLOGY:

• ANCA-associated vasculitis is a rare and complex autoimmune disease that is traditionally classified into granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA).
• Researchers employed advanced artificial intelligence and big data techniques to identify phenotypically distinct subgroups of ANCA-associated vasculitis and developed a classification system using real-world patient data from the Federated Vasculitis Registry consortium.
• They included 3868 patients diagnosed with ANCA-associated vasculitis between November 1, 1966, and March 1, 2023 (mean age at diagnosis, 57.2 years; 51.9% men), across six European vasculitis registries; while a majority of patients (62.9%) were diagnosed with GPA, the remaining 37.1% were diagnosed with MPA.
• Overall, 17 clinical and demographic variables such as the age at diagnosis, gender, serum creatinine and C-reactive protein levels, the type of ANCA, and the involvement of various organ systems were used to create a model for categorizing patients into different clusters.
• The median follow-up duration was 4.2 years.

TAKEAWAY:

• Five distinct clusters were identified in ANCA-associated vasculitis; three had significant kidney involvement (the severe kidney cluster, myeloperoxidase-ANCA-positive kidney cluster, and proteinase 3-ANCA-positive kidney cluster) and two had minimal kidney involvement (young respiratory cluster and inflammatory multisystem cluster).
• The clusters with significant kidney involvement were associated with poorer outcomes, including a higher risk for kidney failure and death. The severe kidney cluster had the poorest prognosis, with mortality and the rate of end-stage kidney failure being 30.5% and 41.6%, respectively.
• The young respiratory cluster, characterized by predominant ear-nose-throat involvement and low systemic inflammation, showed the best prognostic outcomes.
• This cluster membership model showed a greater predictive accuracy for patient and kidney survival than traditional methods based on clinical diagnosis or ANCA specificity.

IN PRACTICE:

“These findings highlight the necessity of recognizing severe kidney disease at the time of diagnosis as an indicator of poor outcome, thereby necessitating intensified treatment approaches,” experts from the Department of Internal Medicine IV (Nephrology and Hypertension), Medical University of Innsbruck, Austria, wrote in an accompanying editorial published online on August 22, 2024, in The Lancet Rheumatology.

SOURCE:

This study was led by Karl Gisslander, Department of Clinical Sciences, Lund University, Lund, Sweden, and was published online on August 22, 2024, in The Lancet Rheumatology.

LIMITATIONS:

Data on estimated glomerular filtration rate recovery in clusters with kidney disease were lacking. Populations from East Asia, where myeloperoxidase-ANCA positivity is more prevalent, were not included.

DISCLOSURES:

This study received funding from the European Union’s Horizon 2020 research and innovation program under the European Joint Programme on Rare Diseases. Some authors declared serving on advisory boards or receiving grants, contracts, travel support, consulting fees, payments, or honoraria from various pharmaceutical companies and other institutions.

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.

VIENNA — Physicians are called to record clinical details of patients with asthma undergoing biologic therapy to monitor clinical remission and keep an eye on eosinophilic granulomatosis with polyangiitis (EGPA) symptoms as patients come off the medications, according to pulmonary experts presenting at the European Respiratory Society (ERS) 2024 International Congress.

Biologics have revolutionized the treatment of severe asthma, significantly improving patient outcomes. However, the focus has recently shifted toward achieving more comprehensive disease control. Remission, already a well-established goal in conditions like rheumatoid arthritis and inflammatory bowel disease, is now being explored in patients with asthma receiving biologics.

Peter Howarth, medical director at Global Medical, Specialty Medicine, GSK, in Brentford, England, said that new clinical remission criteria in asthma may be overly rigid and of little use. He said that more attainable limits must be created. Meanwhile, clinicians should collect clinical data more thoroughly.

In parallel, studies have also raised questions about the role of biologics in the emergence of EGPA.
 

Defining Clinical Remission in Asthma

Last year, a working group, including members from the American Thoracic Society and the American College and Academy of Allergy, Asthma, and Immunology, proposed new guidelines to define clinical remission in asthma. These guidelines extended beyond the typical outcomes of no severe exacerbations, no maintenance oral corticosteroid use, good asthma control, and stable lung function. The additional recommendations included no missed work or school due to asthma, limited use of rescue medication (no more than once a month), and reduced inhaled corticosteroid use to low or medium doses.

To explore the feasibility of achieving these clinical remission outcomes, GSK partnered with the Mayo Clinic for a retrospective analysis of the medical records of 700 patients with asthma undergoing various biologic therapies. The study revealed that essential data for determining clinical remission, such as asthma control and exacerbation records, were inconsistently documented. While some data were recorded, such as maintenance corticosteroid use in 50%-60% of cases, other key measures, like asthma control, were recorded in less than a quarter of the patients.

GSK researchers analyzed available data and found that around 30% of patients on any biologic therapy met three components of remission. Mepolizumab performed better than other corticosteroids, with over 40% of those receiving the drug meeting these criteria. However, when stricter definitions were applied, such as requiring four or more remission components, fewer patients achieved remission — less than 10% for four components, with no patients meeting the full seven-point criteria proposed by the working group.

An ongoing ERS Task Force is now exploring what clinical remission outcomes are practical to achieve, as the current definitions may be too aspirational, said Mr. Howarth. “It’s a matter of defying what is practical to achieve because if you can’t achieve it, then it won’t be valuable.”

He also pointed out that biologics are often used for the most severe cases of asthma after other treatments have failed. Evidence suggests that introducing biologics earlier in the disease, before chronic damage occurs, may result in better patient outcomes.
 

Biologics and EGPA

In a retrospective study, clinical details of 27 patients with adult-onset asthma from 28 countries, all on biologic therapy, were analyzed. The study, a multicounty collaboration, was led by ERS Severe Heterogeneous Asthma Research Collaboration, Patient-centred (SHARP), and aimed to understand the role of biologics in the emergence of EGPA.

The most significant finding presented at the ERS 2024 International Congress was that EGPA was not associated with maintenance corticosteroids; instead, it often emerged when corticosteroid doses were reduced or tapered off. “This might suggest that steroid withdrawal may unmask the underlying disease,” said Hitasha Rupani, MD, a consultant respiratory physician at the University Hospital Southampton, in Southampton, England. Importantly, the rate at which steroids were tapered did not influence the onset of EGPA, indicating that the tapering process, rather than its speed, may be the critical factor. However, due to the small sample size, this remains a hypothesis, Dr. Rupani explained.

The study also found that when clinicians had a clinical suspicion of EGPA before starting biologic therapy, the diagnosis was made earlier than in cases without such suspicion. Dr. Rupani concluded that this underscores the importance of clinical vigilance and the need to monitor patients closely for EGPA symptoms, especially during corticosteroid tapering.

The study was funded by GSK. Mr. Howarth is an employee at GSK. Dr. Rupani reports no relevant financial relationships. 

A version of this article appeared on Medscape.com.

VIENNA — Physicians are called to record clinical details of patients with asthma undergoing biologic therapy to monitor clinical remission and keep an eye on eosinophilic granulomatosis with polyangiitis (EGPA) symptoms as patients come off the medications, according to pulmonary experts presenting at the European Respiratory Society (ERS) 2024 International Congress.

Biologics have revolutionized the treatment of severe asthma, significantly improving patient outcomes. However, the focus has recently shifted toward achieving more comprehensive disease control. Remission, already a well-established goal in conditions like rheumatoid arthritis and inflammatory bowel disease, is now being explored in patients with asthma receiving biologics.

Peter Howarth, medical director at Global Medical, Specialty Medicine, GSK, in Brentford, England, said that new clinical remission criteria in asthma may be overly rigid and of little use. He said that more attainable limits must be created. Meanwhile, clinicians should collect clinical data more thoroughly.

In parallel, studies have also raised questions about the role of biologics in the emergence of EGPA.
 

Defining Clinical Remission in Asthma

Last year, a working group, including members from the American Thoracic Society and the American College and Academy of Allergy, Asthma, and Immunology, proposed new guidelines to define clinical remission in asthma. These guidelines extended beyond the typical outcomes of no severe exacerbations, no maintenance oral corticosteroid use, good asthma control, and stable lung function. The additional recommendations included no missed work or school due to asthma, limited use of rescue medication (no more than once a month), and reduced inhaled corticosteroid use to low or medium doses.

To explore the feasibility of achieving these clinical remission outcomes, GSK partnered with the Mayo Clinic for a retrospective analysis of the medical records of 700 patients with asthma undergoing various biologic therapies. The study revealed that essential data for determining clinical remission, such as asthma control and exacerbation records, were inconsistently documented. While some data were recorded, such as maintenance corticosteroid use in 50%-60% of cases, other key measures, like asthma control, were recorded in less than a quarter of the patients.

GSK researchers analyzed available data and found that around 30% of patients on any biologic therapy met three components of remission. Mepolizumab performed better than other corticosteroids, with over 40% of those receiving the drug meeting these criteria. However, when stricter definitions were applied, such as requiring four or more remission components, fewer patients achieved remission — less than 10% for four components, with no patients meeting the full seven-point criteria proposed by the working group.

An ongoing ERS Task Force is now exploring what clinical remission outcomes are practical to achieve, as the current definitions may be too aspirational, said Mr. Howarth. “It’s a matter of defying what is practical to achieve because if you can’t achieve it, then it won’t be valuable.”

He also pointed out that biologics are often used for the most severe cases of asthma after other treatments have failed. Evidence suggests that introducing biologics earlier in the disease, before chronic damage occurs, may result in better patient outcomes.
 

Biologics and EGPA

In a retrospective study, clinical details of 27 patients with adult-onset asthma from 28 countries, all on biologic therapy, were analyzed. The study, a multicounty collaboration, was led by ERS Severe Heterogeneous Asthma Research Collaboration, Patient-centred (SHARP), and aimed to understand the role of biologics in the emergence of EGPA.

The most significant finding presented at the ERS 2024 International Congress was that EGPA was not associated with maintenance corticosteroids; instead, it often emerged when corticosteroid doses were reduced or tapered off. “This might suggest that steroid withdrawal may unmask the underlying disease,” said Hitasha Rupani, MD, a consultant respiratory physician at the University Hospital Southampton, in Southampton, England. Importantly, the rate at which steroids were tapered did not influence the onset of EGPA, indicating that the tapering process, rather than its speed, may be the critical factor. However, due to the small sample size, this remains a hypothesis, Dr. Rupani explained.

The study also found that when clinicians had a clinical suspicion of EGPA before starting biologic therapy, the diagnosis was made earlier than in cases without such suspicion. Dr. Rupani concluded that this underscores the importance of clinical vigilance and the need to monitor patients closely for EGPA symptoms, especially during corticosteroid tapering.

The study was funded by GSK. Mr. Howarth is an employee at GSK. Dr. Rupani reports no relevant financial relationships. 

A version of this article appeared on Medscape.com.

VIENNA — Physicians are called to record clinical details of patients with asthma undergoing biologic therapy to monitor clinical remission and keep an eye on eosinophilic granulomatosis with polyangiitis (EGPA) symptoms as patients come off the medications, according to pulmonary experts presenting at the European Respiratory Society (ERS) 2024 International Congress.

Biologics have revolutionized the treatment of severe asthma, significantly improving patient outcomes. However, the focus has recently shifted toward achieving more comprehensive disease control. Remission, already a well-established goal in conditions like rheumatoid arthritis and inflammatory bowel disease, is now being explored in patients with asthma receiving biologics.

Peter Howarth, medical director at Global Medical, Specialty Medicine, GSK, in Brentford, England, said that new clinical remission criteria in asthma may be overly rigid and of little use. He said that more attainable limits must be created. Meanwhile, clinicians should collect clinical data more thoroughly.

In parallel, studies have also raised questions about the role of biologics in the emergence of EGPA.
 

Defining Clinical Remission in Asthma

Last year, a working group, including members from the American Thoracic Society and the American College and Academy of Allergy, Asthma, and Immunology, proposed new guidelines to define clinical remission in asthma. These guidelines extended beyond the typical outcomes of no severe exacerbations, no maintenance oral corticosteroid use, good asthma control, and stable lung function. The additional recommendations included no missed work or school due to asthma, limited use of rescue medication (no more than once a month), and reduced inhaled corticosteroid use to low or medium doses.

To explore the feasibility of achieving these clinical remission outcomes, GSK partnered with the Mayo Clinic for a retrospective analysis of the medical records of 700 patients with asthma undergoing various biologic therapies. The study revealed that essential data for determining clinical remission, such as asthma control and exacerbation records, were inconsistently documented. While some data were recorded, such as maintenance corticosteroid use in 50%-60% of cases, other key measures, like asthma control, were recorded in less than a quarter of the patients.

GSK researchers analyzed available data and found that around 30% of patients on any biologic therapy met three components of remission. Mepolizumab performed better than other corticosteroids, with over 40% of those receiving the drug meeting these criteria. However, when stricter definitions were applied, such as requiring four or more remission components, fewer patients achieved remission — less than 10% for four components, with no patients meeting the full seven-point criteria proposed by the working group.

An ongoing ERS Task Force is now exploring what clinical remission outcomes are practical to achieve, as the current definitions may be too aspirational, said Mr. Howarth. “It’s a matter of defying what is practical to achieve because if you can’t achieve it, then it won’t be valuable.”

He also pointed out that biologics are often used for the most severe cases of asthma after other treatments have failed. Evidence suggests that introducing biologics earlier in the disease, before chronic damage occurs, may result in better patient outcomes.
 

Biologics and EGPA

In a retrospective study, clinical details of 27 patients with adult-onset asthma from 28 countries, all on biologic therapy, were analyzed. The study, a multicounty collaboration, was led by ERS Severe Heterogeneous Asthma Research Collaboration, Patient-centred (SHARP), and aimed to understand the role of biologics in the emergence of EGPA.

The most significant finding presented at the ERS 2024 International Congress was that EGPA was not associated with maintenance corticosteroids; instead, it often emerged when corticosteroid doses were reduced or tapered off. “This might suggest that steroid withdrawal may unmask the underlying disease,” said Hitasha Rupani, MD, a consultant respiratory physician at the University Hospital Southampton, in Southampton, England. Importantly, the rate at which steroids were tapered did not influence the onset of EGPA, indicating that the tapering process, rather than its speed, may be the critical factor. However, due to the small sample size, this remains a hypothesis, Dr. Rupani explained.

The study also found that when clinicians had a clinical suspicion of EGPA before starting biologic therapy, the diagnosis was made earlier than in cases without such suspicion. Dr. Rupani concluded that this underscores the importance of clinical vigilance and the need to monitor patients closely for EGPA symptoms, especially during corticosteroid tapering.

The study was funded by GSK. Mr. Howarth is an employee at GSK. Dr. Rupani reports no relevant financial relationships. 

A version of this article appeared on Medscape.com.

TOPLINE:

Exposure to environmental particulate matter ≤ 10 μm in diameter (PM₁₀) is associated with an increased risk for giant cell arteritis, particularly in older individuals aged ≥ 70 years and those with prolonged exposure to high levels of air pollution.

METHODOLOGY:

• Researchers conducted a retrospective case-crossover study to examine the association between exposure to airborne PM₁₀ and the risk for giant cell arteritis and its ischemic complications.
• They included 232 patients with giant cell arteritis (median age at diagnosis, 73 years; 69% women) from three hospitals in northern Italy between June 2013 to December 2021.
• The hourly and daily average concentrations of PM₁₀ were collected from the Italian monitoring network; patients’ exposure to PM₁₀ was calculated using a space-time statistical model, incorporating meteorological variables, elevation, and proximity to main roads.
• The mean follow-up time of this cohort was 38 months.

TAKEAWAY:

• Every 10 μg/m³ increase in PM₁₀ exposure in the preceding 60 days increased the incremental risk (IR) for giant cell arteritis by 27.1% (95% CI, 5.8-52.6).
• This association was more pronounced (IR, 38.8%; 95% CI, 9.2-76.3) in the subgroup of patients aged ≥ 70 years.
• The positive association between incident giant cell arteritis and concentrations of PM₁₀ was seen only when patients were exposed to high concentrations of PM₁₀ (26.9 ± 13.8 μg/m³) but not low concentrations (11.9 ± 7.9 μg/m³).
• This study did not show any significant association between exposure to PM₁₀ and ischemic complications.

IN PRACTICE:

“Exposure to PM₁₀ in the 60 days preceding [giant cell arteritis] symptoms onset seems to be associated with an increased risk of developing the disease, especially in older individuals with prolonged exposure to high levels of air pollution,” the authors wrote.

SOURCE:

The study was led by Milena Bond, MD, Hospital of Bruneck, Teaching Hospital of the Paracelsus Medical University, Brunico, Italy, and was published online in Arthritis Care & Research.

LIMITATIONS:

The retrospective nature of the study may have introduced recall bias. The study did not include data for other particulate matter fractions or gaseous pollutants, which may have impacted the findings. The use of residential addresses at the time of diagnosis precluded assessment of potential recent relocations.

DISCLOSURES:

This study did not disclose any funding source. Some authors reported having financial relationships with multiple pharmaceutical companies.

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:

Exposure to environmental particulate matter ≤ 10 μm in diameter (PM₁₀) is associated with an increased risk for giant cell arteritis, particularly in older individuals aged ≥ 70 years and those with prolonged exposure to high levels of air pollution.

METHODOLOGY:

• Researchers conducted a retrospective case-crossover study to examine the association between exposure to airborne PM₁₀ and the risk for giant cell arteritis and its ischemic complications.
• They included 232 patients with giant cell arteritis (median age at diagnosis, 73 years; 69% women) from three hospitals in northern Italy between June 2013 to December 2021.
• The hourly and daily average concentrations of PM₁₀ were collected from the Italian monitoring network; patients’ exposure to PM₁₀ was calculated using a space-time statistical model, incorporating meteorological variables, elevation, and proximity to main roads.
• The mean follow-up time of this cohort was 38 months.

TAKEAWAY:

• Every 10 μg/m³ increase in PM₁₀ exposure in the preceding 60 days increased the incremental risk (IR) for giant cell arteritis by 27.1% (95% CI, 5.8-52.6).
• This association was more pronounced (IR, 38.8%; 95% CI, 9.2-76.3) in the subgroup of patients aged ≥ 70 years.
• The positive association between incident giant cell arteritis and concentrations of PM₁₀ was seen only when patients were exposed to high concentrations of PM₁₀ (26.9 ± 13.8 μg/m³) but not low concentrations (11.9 ± 7.9 μg/m³).
• This study did not show any significant association between exposure to PM₁₀ and ischemic complications.

IN PRACTICE:

“Exposure to PM₁₀ in the 60 days preceding [giant cell arteritis] symptoms onset seems to be associated with an increased risk of developing the disease, especially in older individuals with prolonged exposure to high levels of air pollution,” the authors wrote.

SOURCE:

The study was led by Milena Bond, MD, Hospital of Bruneck, Teaching Hospital of the Paracelsus Medical University, Brunico, Italy, and was published online in Arthritis Care & Research.

LIMITATIONS:

The retrospective nature of the study may have introduced recall bias. The study did not include data for other particulate matter fractions or gaseous pollutants, which may have impacted the findings. The use of residential addresses at the time of diagnosis precluded assessment of potential recent relocations.

DISCLOSURES:

This study did not disclose any funding source. Some authors reported having financial relationships with multiple pharmaceutical companies.

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:

Exposure to environmental particulate matter ≤ 10 μm in diameter (PM₁₀) is associated with an increased risk for giant cell arteritis, particularly in older individuals aged ≥ 70 years and those with prolonged exposure to high levels of air pollution.

METHODOLOGY:

• Researchers conducted a retrospective case-crossover study to examine the association between exposure to airborne PM₁₀ and the risk for giant cell arteritis and its ischemic complications.
• They included 232 patients with giant cell arteritis (median age at diagnosis, 73 years; 69% women) from three hospitals in northern Italy between June 2013 to December 2021.
• The hourly and daily average concentrations of PM₁₀ were collected from the Italian monitoring network; patients’ exposure to PM₁₀ was calculated using a space-time statistical model, incorporating meteorological variables, elevation, and proximity to main roads.
• The mean follow-up time of this cohort was 38 months.

TAKEAWAY:

• Every 10 μg/m³ increase in PM₁₀ exposure in the preceding 60 days increased the incremental risk (IR) for giant cell arteritis by 27.1% (95% CI, 5.8-52.6).
• This association was more pronounced (IR, 38.8%; 95% CI, 9.2-76.3) in the subgroup of patients aged ≥ 70 years.
• The positive association between incident giant cell arteritis and concentrations of PM₁₀ was seen only when patients were exposed to high concentrations of PM₁₀ (26.9 ± 13.8 μg/m³) but not low concentrations (11.9 ± 7.9 μg/m³).
• This study did not show any significant association between exposure to PM₁₀ and ischemic complications.

IN PRACTICE:

“Exposure to PM₁₀ in the 60 days preceding [giant cell arteritis] symptoms onset seems to be associated with an increased risk of developing the disease, especially in older individuals with prolonged exposure to high levels of air pollution,” the authors wrote.

SOURCE:

The study was led by Milena Bond, MD, Hospital of Bruneck, Teaching Hospital of the Paracelsus Medical University, Brunico, Italy, and was published online in Arthritis Care & Research.

LIMITATIONS:

The retrospective nature of the study may have introduced recall bias. The study did not include data for other particulate matter fractions or gaseous pollutants, which may have impacted the findings. The use of residential addresses at the time of diagnosis precluded assessment of potential recent relocations.

DISCLOSURES:

This study did not disclose any funding source. Some authors reported having financial relationships with multiple pharmaceutical companies.

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.

New treatment strategies in clinical trials show promise in reducing the tapering time of glucocorticoids (GCs) or possibly even replacing the use of GCs. Selective GC receptor agonists and modulators and GC plus hydroxysteroid dehydrogenase inhibitor combination therapy are some of the approaches under consideration.

“There is growing observational data that confirms the GC-sparing effect seen in some of these clinical trials in real-world data,” said Sebastian E. Sattui, MD, assistant professor of medicine and director of the Vasculitis Center at the University of Pittsburgh Medical Center, Pittsburgh.

GC minimization is an important goal, “and the data emerging from these trials should be reassuring for rheumatology providers,” Dr. Sattui said.

HSD-1 Inhibitors Under Study

11ß-Hydroxysteroid dehydrogenase type 1 (11ß-HSD1) is a tissue-specific intracellular modulator of GC action that’s been trialed for a number of rheumatic conditions. “HSD-1 deficiency or inhibition has been consistently associated with reduced GC side effects in mouse and human,” wrote the authors of a study testing the coadministration of HSD-1 inhibitor SPI-62 (clofutriben) with prednisolone in patients with polymyalgia rheumatica (PMR) to measure its impact on efficacy and toxicity.

Lead study author David Katz, PhD, chief scientific officer at Sparrow Pharmaceuticals, presented results at the at the annual European Congress of Rheumatology.

GCs are often the first-line therapy with PMR. However, it’s very difficult for patients to stop taking GCs once they start taking them. The study included patients with PMR who were taking 10 mg/d prednisolone and didn’t require a dose increase. For the study, they continued prednisolone without dose reduction for 4 weeks, receiving either SPI-62 6 mg/d or a matching placebo for 2 weeks.

During SPI-62 treatment, researchers in sequential cohorts maintained daily prednisolone doses at 10 mg, adjusted to 15 mg or adjusted to 20 mg.

A 10-mg dose of prednisolone combined with 6 mg of SPI-62 demonstrated less efficacy compared with placebo but improved upon prednisolone toxicities such as bone formation and resorption biomarkers, lipidemia, and insulin resistance. Doubling the dose to 20 mg prednisolone combined with SPI-62 achieved similar efficacy and maintained improvement of prednisolone toxicity markers.

“In patients with PMR, when we double the dose of prednisolone during coadministration with a potent HSD-1 inhibitor, we are able to have similar stability of symptoms, physical function, and systemic inflammation. At the same time, we are able to show improvements on biomarkers of bone turnover and insulin resistance,” Dr. Katz informed the EULAR 2024 audience.

An ongoing phase 2 clinical trial is testing SPI-62 in patients with endogenous Cushing syndrome. “It’s a longer-term trial, so we’re able to see at least an individual patient’s more clinical outcomes such as reversal of Cushing’s-associated myopathy and the ability of patients to discontinue all of their antidiabetic medications and yet still have good glycemic control,” he said.

Another research team from the United Kingdom explored whether AZD4017, an inhibitor of human 11ß-HSD1, could mitigate GC effects. The researchers randomly assigned 32 healthy male volunteers to AZD4017 or placebo, along with prednisolone. They reported a worsening of hepatic insulin sensitivity in the placebo group but not in the AZD4017 group, and protective effects of AZD4017 on markers of lipid metabolism and bone turnover, as well as lowered nighttime blood pressure. The results signified that coadministration of AZD4017 with prednisolone in men could be a way to reduce GC side effects.

In a Japanese phase 1/2 study, 11ß-HSD1 inhibitor S-707106 proved useful as an insulin sensitizer and antisarcopenic and anti-obesity medication in 16 patients with Cushing syndrome and autonomous cortisol secretion.
 

Novel Antitumor Necrosis Factor (TNF) Antibody Plus GC Receptor Modulator Conjugate

A novel antibody-drug conjugate comprising the anti-TNF monoclonal antibody adalimumab (ABBV-3373) linked to a GC receptor modulator shows promise as a GC alternative.

A notable 2022 study authored by Frank Buttgereit, MD, and other researchers assessed its safety and efficacy in a randomized, double-blind, active-controlled, proof-of-concept trial.

ABBV-3373 “was designed to potentially allow precise targeting of activated immune cells while significantly dampening inflammation and minimizing the systemic side effects associated with glucocorticoids,” according to AbbVie, its manufacturer.

A total of 48 adults with moderate to severe rheumatoid arthritis receiving background methotrexate were randomized to receive either ABBV-3373 (n = 31) or adalimumab (n = 17). The novel drug at 12 weeks showed a −2.65 reduction in the Disease Activity Score in 28 joints using C-reactive protein, compared with −2.13 for adalimumab. Researchers also predicted ABBV-3373 to be more effective than adalimumab based on in-trial and historical adalimumab data.

“We have great expectations for this molecule,” said Giovanni Adami, MD, PhD, a rheumatologist at the University of Verona, Verona, Italy, who has coauthored several studies on the use of GCs. Plans are underway for a phase 3 study with ABBV-3373.
 

C5a and Interleukin (IL)-6 Receptor Inhibitors as GC-Sparing Drugs

Investigators in a 2021 paper explored whether the C5a receptor inhibitor avacopan could effectively treat patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis without the need for daily GCs, following treatment with either cyclophosphamide or rituximab. They randomized 331 patients to receive avacopan or prednisone given on a tapering schedule for 20 weeks (60 mg/d tapered to discontinuation by week 21). “Avacopan was noninferior but not superior to prednisone taper with respect to remission at week 26 and was superior to prednisone taper with respect to sustained remission at week 52,” the investigators summarized.

A longer trial should test avacopan’s safety and durability in patients with ANCA-associated vasculitis, they recommended.

Sarilumab, a human monoclonal antibody that binds IL-6 receptor alpha and blocks the IL-6 pathway, yielded good results in the phase 3 SAPHYR trial as an alternative for patients with PMR who relapse while tapering prednisone therapy.

Researchers in the SAPHYR trial randomly assigned 118 patients 1:1 to receive a twice-monthly subcutaneous injection of sarilumab over 52 weeks plus a 14-week prednisone taper or placebo plus a 52-week prednisone taper. Patients in each group received a tapered GC dose initially at 15 mg/d for 2 weeks in a blinded fashion to control for disease at baseline.

Sarilumab effectively sustained remission in patients, significantly reducing the GC dose compared with placebo.

Disease flare after clinical remission took place in 57% of patients in the placebo group, vs 24% in the sarilumab group. “The placebo-treated patients had a fairly traditional 52-week GC taper. The patients treated with sarilumab had a very rapid GC taper,” said lead study author Robert Spiera, MD, director of the Scleroderma, Vasculitis and Myositis Center at the Hospital for Special Surgery, New York City.

In his own practice, Dr. Spiera often treats his patients with new-onset PMR with a fairly rapid GC taper, akin to what was used in SAPHYR, recognizing that a portion of these patients can be successfully treated with a relatively brief course of GCs, although the majority will need to have “rescue” therapy for flares with that approach.

Hospital for Special Surgery

A version of this article appeared on Medscape.com.

New treatment strategies in clinical trials show promise in reducing the tapering time of glucocorticoids (GCs) or possibly even replacing the use of GCs. Selective GC receptor agonists and modulators and GC plus hydroxysteroid dehydrogenase inhibitor combination therapy are some of the approaches under consideration.

“There is growing observational data that confirms the GC-sparing effect seen in some of these clinical trials in real-world data,” said Sebastian E. Sattui, MD, assistant professor of medicine and director of the Vasculitis Center at the University of Pittsburgh Medical Center, Pittsburgh.

GC minimization is an important goal, “and the data emerging from these trials should be reassuring for rheumatology providers,” Dr. Sattui said.

HSD-1 Inhibitors Under Study

11ß-Hydroxysteroid dehydrogenase type 1 (11ß-HSD1) is a tissue-specific intracellular modulator of GC action that’s been trialed for a number of rheumatic conditions. “HSD-1 deficiency or inhibition has been consistently associated with reduced GC side effects in mouse and human,” wrote the authors of a study testing the coadministration of HSD-1 inhibitor SPI-62 (clofutriben) with prednisolone in patients with polymyalgia rheumatica (PMR) to measure its impact on efficacy and toxicity.

Lead study author David Katz, PhD, chief scientific officer at Sparrow Pharmaceuticals, presented results at the at the annual European Congress of Rheumatology.

GCs are often the first-line therapy with PMR. However, it’s very difficult for patients to stop taking GCs once they start taking them. The study included patients with PMR who were taking 10 mg/d prednisolone and didn’t require a dose increase. For the study, they continued prednisolone without dose reduction for 4 weeks, receiving either SPI-62 6 mg/d or a matching placebo for 2 weeks.

During SPI-62 treatment, researchers in sequential cohorts maintained daily prednisolone doses at 10 mg, adjusted to 15 mg or adjusted to 20 mg.

A 10-mg dose of prednisolone combined with 6 mg of SPI-62 demonstrated less efficacy compared with placebo but improved upon prednisolone toxicities such as bone formation and resorption biomarkers, lipidemia, and insulin resistance. Doubling the dose to 20 mg prednisolone combined with SPI-62 achieved similar efficacy and maintained improvement of prednisolone toxicity markers.

“In patients with PMR, when we double the dose of prednisolone during coadministration with a potent HSD-1 inhibitor, we are able to have similar stability of symptoms, physical function, and systemic inflammation. At the same time, we are able to show improvements on biomarkers of bone turnover and insulin resistance,” Dr. Katz informed the EULAR 2024 audience.

An ongoing phase 2 clinical trial is testing SPI-62 in patients with endogenous Cushing syndrome. “It’s a longer-term trial, so we’re able to see at least an individual patient’s more clinical outcomes such as reversal of Cushing’s-associated myopathy and the ability of patients to discontinue all of their antidiabetic medications and yet still have good glycemic control,” he said.

Another research team from the United Kingdom explored whether AZD4017, an inhibitor of human 11ß-HSD1, could mitigate GC effects. The researchers randomly assigned 32 healthy male volunteers to AZD4017 or placebo, along with prednisolone. They reported a worsening of hepatic insulin sensitivity in the placebo group but not in the AZD4017 group, and protective effects of AZD4017 on markers of lipid metabolism and bone turnover, as well as lowered nighttime blood pressure. The results signified that coadministration of AZD4017 with prednisolone in men could be a way to reduce GC side effects.

In a Japanese phase 1/2 study, 11ß-HSD1 inhibitor S-707106 proved useful as an insulin sensitizer and antisarcopenic and anti-obesity medication in 16 patients with Cushing syndrome and autonomous cortisol secretion.
 

Novel Antitumor Necrosis Factor (TNF) Antibody Plus GC Receptor Modulator Conjugate

A novel antibody-drug conjugate comprising the anti-TNF monoclonal antibody adalimumab (ABBV-3373) linked to a GC receptor modulator shows promise as a GC alternative.

A notable 2022 study authored by Frank Buttgereit, MD, and other researchers assessed its safety and efficacy in a randomized, double-blind, active-controlled, proof-of-concept trial.

ABBV-3373 “was designed to potentially allow precise targeting of activated immune cells while significantly dampening inflammation and minimizing the systemic side effects associated with glucocorticoids,” according to AbbVie, its manufacturer.

A total of 48 adults with moderate to severe rheumatoid arthritis receiving background methotrexate were randomized to receive either ABBV-3373 (n = 31) or adalimumab (n = 17). The novel drug at 12 weeks showed a −2.65 reduction in the Disease Activity Score in 28 joints using C-reactive protein, compared with −2.13 for adalimumab. Researchers also predicted ABBV-3373 to be more effective than adalimumab based on in-trial and historical adalimumab data.

“We have great expectations for this molecule,” said Giovanni Adami, MD, PhD, a rheumatologist at the University of Verona, Verona, Italy, who has coauthored several studies on the use of GCs. Plans are underway for a phase 3 study with ABBV-3373.
 

C5a and Interleukin (IL)-6 Receptor Inhibitors as GC-Sparing Drugs

Investigators in a 2021 paper explored whether the C5a receptor inhibitor avacopan could effectively treat patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis without the need for daily GCs, following treatment with either cyclophosphamide or rituximab. They randomized 331 patients to receive avacopan or prednisone given on a tapering schedule for 20 weeks (60 mg/d tapered to discontinuation by week 21). “Avacopan was noninferior but not superior to prednisone taper with respect to remission at week 26 and was superior to prednisone taper with respect to sustained remission at week 52,” the investigators summarized.

A longer trial should test avacopan’s safety and durability in patients with ANCA-associated vasculitis, they recommended.

Sarilumab, a human monoclonal antibody that binds IL-6 receptor alpha and blocks the IL-6 pathway, yielded good results in the phase 3 SAPHYR trial as an alternative for patients with PMR who relapse while tapering prednisone therapy.

Researchers in the SAPHYR trial randomly assigned 118 patients 1:1 to receive a twice-monthly subcutaneous injection of sarilumab over 52 weeks plus a 14-week prednisone taper or placebo plus a 52-week prednisone taper. Patients in each group received a tapered GC dose initially at 15 mg/d for 2 weeks in a blinded fashion to control for disease at baseline.

Sarilumab effectively sustained remission in patients, significantly reducing the GC dose compared with placebo.

Disease flare after clinical remission took place in 57% of patients in the placebo group, vs 24% in the sarilumab group. “The placebo-treated patients had a fairly traditional 52-week GC taper. The patients treated with sarilumab had a very rapid GC taper,” said lead study author Robert Spiera, MD, director of the Scleroderma, Vasculitis and Myositis Center at the Hospital for Special Surgery, New York City.

In his own practice, Dr. Spiera often treats his patients with new-onset PMR with a fairly rapid GC taper, akin to what was used in SAPHYR, recognizing that a portion of these patients can be successfully treated with a relatively brief course of GCs, although the majority will need to have “rescue” therapy for flares with that approach.

Hospital for Special Surgery

A version of this article appeared on Medscape.com.

New treatment strategies in clinical trials show promise in reducing the tapering time of glucocorticoids (GCs) or possibly even replacing the use of GCs. Selective GC receptor agonists and modulators and GC plus hydroxysteroid dehydrogenase inhibitor combination therapy are some of the approaches under consideration.

“There is growing observational data that confirms the GC-sparing effect seen in some of these clinical trials in real-world data,” said Sebastian E. Sattui, MD, assistant professor of medicine and director of the Vasculitis Center at the University of Pittsburgh Medical Center, Pittsburgh.

GC minimization is an important goal, “and the data emerging from these trials should be reassuring for rheumatology providers,” Dr. Sattui said.

HSD-1 Inhibitors Under Study

11ß-Hydroxysteroid dehydrogenase type 1 (11ß-HSD1) is a tissue-specific intracellular modulator of GC action that’s been trialed for a number of rheumatic conditions. “HSD-1 deficiency or inhibition has been consistently associated with reduced GC side effects in mouse and human,” wrote the authors of a study testing the coadministration of HSD-1 inhibitor SPI-62 (clofutriben) with prednisolone in patients with polymyalgia rheumatica (PMR) to measure its impact on efficacy and toxicity.

Lead study author David Katz, PhD, chief scientific officer at Sparrow Pharmaceuticals, presented results at the at the annual European Congress of Rheumatology.

GCs are often the first-line therapy with PMR. However, it’s very difficult for patients to stop taking GCs once they start taking them. The study included patients with PMR who were taking 10 mg/d prednisolone and didn’t require a dose increase. For the study, they continued prednisolone without dose reduction for 4 weeks, receiving either SPI-62 6 mg/d or a matching placebo for 2 weeks.

During SPI-62 treatment, researchers in sequential cohorts maintained daily prednisolone doses at 10 mg, adjusted to 15 mg or adjusted to 20 mg.

A 10-mg dose of prednisolone combined with 6 mg of SPI-62 demonstrated less efficacy compared with placebo but improved upon prednisolone toxicities such as bone formation and resorption biomarkers, lipidemia, and insulin resistance. Doubling the dose to 20 mg prednisolone combined with SPI-62 achieved similar efficacy and maintained improvement of prednisolone toxicity markers.

“In patients with PMR, when we double the dose of prednisolone during coadministration with a potent HSD-1 inhibitor, we are able to have similar stability of symptoms, physical function, and systemic inflammation. At the same time, we are able to show improvements on biomarkers of bone turnover and insulin resistance,” Dr. Katz informed the EULAR 2024 audience.

An ongoing phase 2 clinical trial is testing SPI-62 in patients with endogenous Cushing syndrome. “It’s a longer-term trial, so we’re able to see at least an individual patient’s more clinical outcomes such as reversal of Cushing’s-associated myopathy and the ability of patients to discontinue all of their antidiabetic medications and yet still have good glycemic control,” he said.

Another research team from the United Kingdom explored whether AZD4017, an inhibitor of human 11ß-HSD1, could mitigate GC effects. The researchers randomly assigned 32 healthy male volunteers to AZD4017 or placebo, along with prednisolone. They reported a worsening of hepatic insulin sensitivity in the placebo group but not in the AZD4017 group, and protective effects of AZD4017 on markers of lipid metabolism and bone turnover, as well as lowered nighttime blood pressure. The results signified that coadministration of AZD4017 with prednisolone in men could be a way to reduce GC side effects.

In a Japanese phase 1/2 study, 11ß-HSD1 inhibitor S-707106 proved useful as an insulin sensitizer and antisarcopenic and anti-obesity medication in 16 patients with Cushing syndrome and autonomous cortisol secretion.
 

Novel Antitumor Necrosis Factor (TNF) Antibody Plus GC Receptor Modulator Conjugate

A novel antibody-drug conjugate comprising the anti-TNF monoclonal antibody adalimumab (ABBV-3373) linked to a GC receptor modulator shows promise as a GC alternative.

A notable 2022 study authored by Frank Buttgereit, MD, and other researchers assessed its safety and efficacy in a randomized, double-blind, active-controlled, proof-of-concept trial.

ABBV-3373 “was designed to potentially allow precise targeting of activated immune cells while significantly dampening inflammation and minimizing the systemic side effects associated with glucocorticoids,” according to AbbVie, its manufacturer.

A total of 48 adults with moderate to severe rheumatoid arthritis receiving background methotrexate were randomized to receive either ABBV-3373 (n = 31) or adalimumab (n = 17). The novel drug at 12 weeks showed a −2.65 reduction in the Disease Activity Score in 28 joints using C-reactive protein, compared with −2.13 for adalimumab. Researchers also predicted ABBV-3373 to be more effective than adalimumab based on in-trial and historical adalimumab data.

“We have great expectations for this molecule,” said Giovanni Adami, MD, PhD, a rheumatologist at the University of Verona, Verona, Italy, who has coauthored several studies on the use of GCs. Plans are underway for a phase 3 study with ABBV-3373.
 

C5a and Interleukin (IL)-6 Receptor Inhibitors as GC-Sparing Drugs

Investigators in a 2021 paper explored whether the C5a receptor inhibitor avacopan could effectively treat patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis without the need for daily GCs, following treatment with either cyclophosphamide or rituximab. They randomized 331 patients to receive avacopan or prednisone given on a tapering schedule for 20 weeks (60 mg/d tapered to discontinuation by week 21). “Avacopan was noninferior but not superior to prednisone taper with respect to remission at week 26 and was superior to prednisone taper with respect to sustained remission at week 52,” the investigators summarized.

A longer trial should test avacopan’s safety and durability in patients with ANCA-associated vasculitis, they recommended.

Sarilumab, a human monoclonal antibody that binds IL-6 receptor alpha and blocks the IL-6 pathway, yielded good results in the phase 3 SAPHYR trial as an alternative for patients with PMR who relapse while tapering prednisone therapy.

Researchers in the SAPHYR trial randomly assigned 118 patients 1:1 to receive a twice-monthly subcutaneous injection of sarilumab over 52 weeks plus a 14-week prednisone taper or placebo plus a 52-week prednisone taper. Patients in each group received a tapered GC dose initially at 15 mg/d for 2 weeks in a blinded fashion to control for disease at baseline.

Sarilumab effectively sustained remission in patients, significantly reducing the GC dose compared with placebo.

Disease flare after clinical remission took place in 57% of patients in the placebo group, vs 24% in the sarilumab group. “The placebo-treated patients had a fairly traditional 52-week GC taper. The patients treated with sarilumab had a very rapid GC taper,” said lead study author Robert Spiera, MD, director of the Scleroderma, Vasculitis and Myositis Center at the Hospital for Special Surgery, New York City.

In his own practice, Dr. Spiera often treats his patients with new-onset PMR with a fairly rapid GC taper, akin to what was used in SAPHYR, recognizing that a portion of these patients can be successfully treated with a relatively brief course of GCs, although the majority will need to have “rescue” therapy for flares with that approach.

Hospital for Special Surgery

A version of this article appeared on Medscape.com.

VIENNA — Results from the phase 3 SELECT-GCA study showed that the Janus kinase (JAK) inhibitor upadacitinib (Rinvoq) induces significant and sustained remission in people with new-onset or relapsing giant cell arteritis (GCA).

The primary endpoint of sustained remission — the absence of GCA signs or symptoms from weeks 12 to 52 together with adherence to a steroid-tapering regimen — occurred in 46% of 210 individuals randomly assigned to treatment treated with a once-daily 15-mg dose of upadacitinib and 29% of 105 randomly assigned to placebo (P = .0019).

Nine of the 11 secondary endpoints were also positive for upadacitinib 15 mg vs placebo, and no new safety concerns were identified in a late-breaking abstract presented at the at the annual European Congress of Rheumatology.
 

First JAK Trial in GCA

This is the first trial to look at the use of a JAK inhibitor for the treatment of GCA, and it is addressing a real unmet need, the presenting study investigator Daniel Blockmans, MD, PhD, of University Hospitals Leuven in Belgium, told this news organization.

Glucocorticoids remain the mainstay of treatment, and tocilizumab has been licensed for use, but people don’t always get better or can relapse, he explained.

“I have the impression that these only suppress the disease but do not cure it,” Dr. Blockmans said, adding that “patients get very well soon after these treatments are started, but there are more and more reports that there is a kind of smoldering vasculitis that exists, and this can lead to dilatation of the aorta.”

Upadacitinib inhibits two JAK-dependent cytokines, interleukin 6 and interferon gamma, which have been implicated in the pathogenesis of GCA. The latter could be particularly important, Dr. Blockmans suggested.
 

Study Details

SELECT-GCA is an ongoing multicenter, randomized, double-blind, placebo-controlled study designed to evaluate the safety and efficacy of upadacitinib vs placebo in patients with GCA.

A total of 428 patients have been included: 210 were randomly allocated to treatment with upadacitinib 15 mg, 105 to upadacitinib 7.5 mg, and 105 to placebo. The inclusion of the lower “minimally effective” upadacitinib dose was a requirement of the regulatory authorities, Dr. Blockmans said; the licensed dose in rheumatoid arthritis (RA) is 15 mg.

Dr. Blockmans reported data from the first 52 weeks of the trial during which all patients underwent glucocorticoid tapering — 26 weeks for upadacitinib and 52 weeks for placebo.

No imaging was done in this trial, which Dr. Blockmans said should be considered for future studies.
 

Secondary Endpoints

One of the key secondary endpoints was sustained complete remission, defined as sustained remission plus a normalized erythrocyte sedimentation rate to ≤ 30 mm/h and reducing high-sensitivity C-reactive protein to < 1 mg/dL.

Sustained complete remission occurred in 37% and 16% of patients treated with upadacitinib 15 mg and placebo, respectively (P < .0001).

Additionally, a significantly lower proportion of upadacitinib 15 mg- than placebo-treated patients experienced at least one disease flare through week 52 (34% vs 56%, P = .0014).

Other positive secondary endpoints for upadacitinib 15 mg vs placebo out to week 52 were the number of disease flares per patient, cumulative glucocorticoid exposure, and complete remission (also at week 24).

And significant changes in SF-36 and FACIT-Fatigue from baseline to week 52 were seen for upadacitinib 15 mg.

The only secondary endpoints not showing a clear benefit for upadacitinib 15 mg were the changes in the Treatment Satisfaction Questionnaire for Medication at 52 weeks and the rate of glucocorticoid-related adverse events through week 52.

As for the 7.5-mg dose of upadacitinib, neither the primary nor secondary endpoints were significantly better vs placebo.
 

‘Life-Changing’

The study’s findings could be “really life-changing” for patients with this type of vasculitis if upadacitinib gets approval for use in this indication, Milena Bond, MD, PhD, of Brunico Hospital in Italy, told this news organization at the meeting.

“Unfortunately, nowadays, we still have only a few options for treating these patients,” she said. “So, this drug could be really, really important.”

Dr. Bond added: “The data ... also shows there is a very good safety profile, which was a main concern given the class of the drug. So, I’m very positive about this treatment and very excited to see the preliminary results.”

After his presentation, Dr. Blockmans said, “Of course, if we already had an ideal treatment for GCA, there would be no need for a JAK inhibitor, but I don’t think that steroid treatment or tocilizumab treatment is the ideal treatment.”
 

Judicious Use Still Warranted

Upadacitinib still needs to be used cautiously, following appropriate guidance from the European Medicines Agency (EMA) and the US Food and Drug Administration.

Dr. Bond said: “It is not advised to use to the drug when people are older than 65 years old,” according to the EMA, for example, and “given the rules that we have, I would not use this drug as a first-line treatment. We do not do that for rheumatoid arthritis.”

But, she added, “As for arthritis, when you fail treating patients with the other alternatives, you could use this drug, and you have to discuss risks with the patients.”

Dr. Blockmans reported there had been no increased risk for major adverse cardiovascular events or venous thromboembolism associated with upadacitinib relative to placebo in the population of patients studied, and he pointed out that they had a much higher risk for these events than perhaps an RA population.

He said: “It’s effective, and it’s apparently safe in these older people, despite what we heard about tofacitinib in the ORAL [Surveillance] study; we didn’t see these problems here in this elderly population.”

The SELECT-GCA trial was funded by AbbVie, and the company participated in all aspects of the study, including its design, conduct, interpretation of data, and reporting. Dr. Blockmans received no funding or other honoraria from the company but reported a research grant from Roche and consulting fees from GlaxoSmithKline. Most of his coauthors reported financial relationships with AbbVie, and some are employees of the company. Dr. Bond reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

VIENNA — Results from the phase 3 SELECT-GCA study showed that the Janus kinase (JAK) inhibitor upadacitinib (Rinvoq) induces significant and sustained remission in people with new-onset or relapsing giant cell arteritis (GCA).

The primary endpoint of sustained remission — the absence of GCA signs or symptoms from weeks 12 to 52 together with adherence to a steroid-tapering regimen — occurred in 46% of 210 individuals randomly assigned to treatment treated with a once-daily 15-mg dose of upadacitinib and 29% of 105 randomly assigned to placebo (P = .0019).

Nine of the 11 secondary endpoints were also positive for upadacitinib 15 mg vs placebo, and no new safety concerns were identified in a late-breaking abstract presented at the at the annual European Congress of Rheumatology.
 

First JAK Trial in GCA

This is the first trial to look at the use of a JAK inhibitor for the treatment of GCA, and it is addressing a real unmet need, the presenting study investigator Daniel Blockmans, MD, PhD, of University Hospitals Leuven in Belgium, told this news organization.

Glucocorticoids remain the mainstay of treatment, and tocilizumab has been licensed for use, but people don’t always get better or can relapse, he explained.

“I have the impression that these only suppress the disease but do not cure it,” Dr. Blockmans said, adding that “patients get very well soon after these treatments are started, but there are more and more reports that there is a kind of smoldering vasculitis that exists, and this can lead to dilatation of the aorta.”

Upadacitinib inhibits two JAK-dependent cytokines, interleukin 6 and interferon gamma, which have been implicated in the pathogenesis of GCA. The latter could be particularly important, Dr. Blockmans suggested.
 

Study Details

SELECT-GCA is an ongoing multicenter, randomized, double-blind, placebo-controlled study designed to evaluate the safety and efficacy of upadacitinib vs placebo in patients with GCA.

A total of 428 patients have been included: 210 were randomly allocated to treatment with upadacitinib 15 mg, 105 to upadacitinib 7.5 mg, and 105 to placebo. The inclusion of the lower “minimally effective” upadacitinib dose was a requirement of the regulatory authorities, Dr. Blockmans said; the licensed dose in rheumatoid arthritis (RA) is 15 mg.

Dr. Blockmans reported data from the first 52 weeks of the trial during which all patients underwent glucocorticoid tapering — 26 weeks for upadacitinib and 52 weeks for placebo.

No imaging was done in this trial, which Dr. Blockmans said should be considered for future studies.
 

Secondary Endpoints

One of the key secondary endpoints was sustained complete remission, defined as sustained remission plus a normalized erythrocyte sedimentation rate to ≤ 30 mm/h and reducing high-sensitivity C-reactive protein to < 1 mg/dL.

Sustained complete remission occurred in 37% and 16% of patients treated with upadacitinib 15 mg and placebo, respectively (P < .0001).

Additionally, a significantly lower proportion of upadacitinib 15 mg- than placebo-treated patients experienced at least one disease flare through week 52 (34% vs 56%, P = .0014).

Other positive secondary endpoints for upadacitinib 15 mg vs placebo out to week 52 were the number of disease flares per patient, cumulative glucocorticoid exposure, and complete remission (also at week 24).

And significant changes in SF-36 and FACIT-Fatigue from baseline to week 52 were seen for upadacitinib 15 mg.

The only secondary endpoints not showing a clear benefit for upadacitinib 15 mg were the changes in the Treatment Satisfaction Questionnaire for Medication at 52 weeks and the rate of glucocorticoid-related adverse events through week 52.

As for the 7.5-mg dose of upadacitinib, neither the primary nor secondary endpoints were significantly better vs placebo.
 

‘Life-Changing’

The study’s findings could be “really life-changing” for patients with this type of vasculitis if upadacitinib gets approval for use in this indication, Milena Bond, MD, PhD, of Brunico Hospital in Italy, told this news organization at the meeting.

“Unfortunately, nowadays, we still have only a few options for treating these patients,” she said. “So, this drug could be really, really important.”

Dr. Bond added: “The data ... also shows there is a very good safety profile, which was a main concern given the class of the drug. So, I’m very positive about this treatment and very excited to see the preliminary results.”

After his presentation, Dr. Blockmans said, “Of course, if we already had an ideal treatment for GCA, there would be no need for a JAK inhibitor, but I don’t think that steroid treatment or tocilizumab treatment is the ideal treatment.”
 

Judicious Use Still Warranted

Upadacitinib still needs to be used cautiously, following appropriate guidance from the European Medicines Agency (EMA) and the US Food and Drug Administration.

Dr. Bond said: “It is not advised to use to the drug when people are older than 65 years old,” according to the EMA, for example, and “given the rules that we have, I would not use this drug as a first-line treatment. We do not do that for rheumatoid arthritis.”

But, she added, “As for arthritis, when you fail treating patients with the other alternatives, you could use this drug, and you have to discuss risks with the patients.”

Dr. Blockmans reported there had been no increased risk for major adverse cardiovascular events or venous thromboembolism associated with upadacitinib relative to placebo in the population of patients studied, and he pointed out that they had a much higher risk for these events than perhaps an RA population.

He said: “It’s effective, and it’s apparently safe in these older people, despite what we heard about tofacitinib in the ORAL [Surveillance] study; we didn’t see these problems here in this elderly population.”

The SELECT-GCA trial was funded by AbbVie, and the company participated in all aspects of the study, including its design, conduct, interpretation of data, and reporting. Dr. Blockmans received no funding or other honoraria from the company but reported a research grant from Roche and consulting fees from GlaxoSmithKline. Most of his coauthors reported financial relationships with AbbVie, and some are employees of the company. Dr. Bond reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

VIENNA — Results from the phase 3 SELECT-GCA study showed that the Janus kinase (JAK) inhibitor upadacitinib (Rinvoq) induces significant and sustained remission in people with new-onset or relapsing giant cell arteritis (GCA).

The primary endpoint of sustained remission — the absence of GCA signs or symptoms from weeks 12 to 52 together with adherence to a steroid-tapering regimen — occurred in 46% of 210 individuals randomly assigned to treatment treated with a once-daily 15-mg dose of upadacitinib and 29% of 105 randomly assigned to placebo (P = .0019).

Nine of the 11 secondary endpoints were also positive for upadacitinib 15 mg vs placebo, and no new safety concerns were identified in a late-breaking abstract presented at the at the annual European Congress of Rheumatology.
 

First JAK Trial in GCA

This is the first trial to look at the use of a JAK inhibitor for the treatment of GCA, and it is addressing a real unmet need, the presenting study investigator Daniel Blockmans, MD, PhD, of University Hospitals Leuven in Belgium, told this news organization.

Glucocorticoids remain the mainstay of treatment, and tocilizumab has been licensed for use, but people don’t always get better or can relapse, he explained.

“I have the impression that these only suppress the disease but do not cure it,” Dr. Blockmans said, adding that “patients get very well soon after these treatments are started, but there are more and more reports that there is a kind of smoldering vasculitis that exists, and this can lead to dilatation of the aorta.”

Upadacitinib inhibits two JAK-dependent cytokines, interleukin 6 and interferon gamma, which have been implicated in the pathogenesis of GCA. The latter could be particularly important, Dr. Blockmans suggested.
 

Study Details

SELECT-GCA is an ongoing multicenter, randomized, double-blind, placebo-controlled study designed to evaluate the safety and efficacy of upadacitinib vs placebo in patients with GCA.

A total of 428 patients have been included: 210 were randomly allocated to treatment with upadacitinib 15 mg, 105 to upadacitinib 7.5 mg, and 105 to placebo. The inclusion of the lower “minimally effective” upadacitinib dose was a requirement of the regulatory authorities, Dr. Blockmans said; the licensed dose in rheumatoid arthritis (RA) is 15 mg.

Dr. Blockmans reported data from the first 52 weeks of the trial during which all patients underwent glucocorticoid tapering — 26 weeks for upadacitinib and 52 weeks for placebo.

No imaging was done in this trial, which Dr. Blockmans said should be considered for future studies.
 

Secondary Endpoints

One of the key secondary endpoints was sustained complete remission, defined as sustained remission plus a normalized erythrocyte sedimentation rate to ≤ 30 mm/h and reducing high-sensitivity C-reactive protein to < 1 mg/dL.

Sustained complete remission occurred in 37% and 16% of patients treated with upadacitinib 15 mg and placebo, respectively (P < .0001).

Additionally, a significantly lower proportion of upadacitinib 15 mg- than placebo-treated patients experienced at least one disease flare through week 52 (34% vs 56%, P = .0014).

Other positive secondary endpoints for upadacitinib 15 mg vs placebo out to week 52 were the number of disease flares per patient, cumulative glucocorticoid exposure, and complete remission (also at week 24).

And significant changes in SF-36 and FACIT-Fatigue from baseline to week 52 were seen for upadacitinib 15 mg.

The only secondary endpoints not showing a clear benefit for upadacitinib 15 mg were the changes in the Treatment Satisfaction Questionnaire for Medication at 52 weeks and the rate of glucocorticoid-related adverse events through week 52.

As for the 7.5-mg dose of upadacitinib, neither the primary nor secondary endpoints were significantly better vs placebo.
 

‘Life-Changing’

The study’s findings could be “really life-changing” for patients with this type of vasculitis if upadacitinib gets approval for use in this indication, Milena Bond, MD, PhD, of Brunico Hospital in Italy, told this news organization at the meeting.

“Unfortunately, nowadays, we still have only a few options for treating these patients,” she said. “So, this drug could be really, really important.”

Dr. Bond added: “The data ... also shows there is a very good safety profile, which was a main concern given the class of the drug. So, I’m very positive about this treatment and very excited to see the preliminary results.”

After his presentation, Dr. Blockmans said, “Of course, if we already had an ideal treatment for GCA, there would be no need for a JAK inhibitor, but I don’t think that steroid treatment or tocilizumab treatment is the ideal treatment.”
 

Judicious Use Still Warranted

Upadacitinib still needs to be used cautiously, following appropriate guidance from the European Medicines Agency (EMA) and the US Food and Drug Administration.

Dr. Bond said: “It is not advised to use to the drug when people are older than 65 years old,” according to the EMA, for example, and “given the rules that we have, I would not use this drug as a first-line treatment. We do not do that for rheumatoid arthritis.”

But, she added, “As for arthritis, when you fail treating patients with the other alternatives, you could use this drug, and you have to discuss risks with the patients.”

Dr. Blockmans reported there had been no increased risk for major adverse cardiovascular events or venous thromboembolism associated with upadacitinib relative to placebo in the population of patients studied, and he pointed out that they had a much higher risk for these events than perhaps an RA population.

He said: “It’s effective, and it’s apparently safe in these older people, despite what we heard about tofacitinib in the ORAL [Surveillance] study; we didn’t see these problems here in this elderly population.”

The SELECT-GCA trial was funded by AbbVie, and the company participated in all aspects of the study, including its design, conduct, interpretation of data, and reporting. Dr. Blockmans received no funding or other honoraria from the company but reported a research grant from Roche and consulting fees from GlaxoSmithKline. Most of his coauthors reported financial relationships with AbbVie, and some are employees of the company. Dr. Bond reported no relevant financial relationships.

A version of this article appeared on Medscape.com.