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Treating nonsevere relapse in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis with an increase in glucocorticoids restores remission but only for a short time, results from the Rituximab in AAV trial show.
The findings identify an important subset of patients with ANCA-associated vasculitis (AAV) who are unable to maintain prolonged remission and may require an alternative treatment approach, wrote investigators in the RAVE-ITN (Rituximab in AAV trial–Immune Tolerance Network) Research Group, led by Dr. John Stone of Massachusetts General Hospital, Boston (Arthritis Rheumatol. 2015 [doi:10.002/art.39104]).
The RAVE study is a randomized, double-blind, placebo-controlled trial comparing rituximab followed by placebo to cyclophosphamide followed by azathioprine for remission induction in patients with ANCA-positive granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). The patients all had severe disease.
Patients who experienced nonsevere relapses between 1 and 18 months were treated with an increased dose of prednisone – without a concomitant change in their non-glucocorticoid immunosuppressants – followed by a taper. The authors defined nonsevere relapses as those with the occurrence of any new disease activity, a Birmingham Vasculitis Activity Score for Wegener’s Granulomatosis (BVAS/WG) of 3 or less, and no major BVAS/WG items.
Of the 44 patients with a first nonsevere relapse, 35 (80%) went into remission following an increase in their prednisone dose.
However 70% of these patients went on to experience a second severe or nonsevere relapse within an average of 6 months.
Only 13 patients (30%) were able to maintain disease-free remission until the end of follow-up, and 8 (18%) were able to do so until their last study visit.
Compared with the 71 patients who maintained relapse-free remission over the study period, patients who were unable to maintain prolonged remission were more likely to have GPA, be PR3-ANCA positive, and have relapsing disease at baseline.
All three of those characteristics occurred in 55% of patients, compared with 30% of patients who maintained remission (P = .01), the researchers reported.
“The high rate of second relapses observed in this subgroup of patients suggests a need for a different treatment paradigm than used in the RAVE trial,” the study authors said.
A coauthor of the study, Dr. Robert F. Spiera, director of the Vasculitis and Scleroderma Program at the Hospital for Special Surgery in New York said the findings suggested that upping the ante in terms of the immunosuppressive therapy beyond steroids should be considered.
In many patients, this may mean re-treating or initiating treatment with rituximab (if they had not previously been treated with that agent for induction of remission), he said, noting that the optimal dose was yet to be defined.
Because patients involved in the current study all had severe disease at trial entry, he advised that the temporary control of relapse that was observed with raising the corticosteroid doses may not apply to patients with nonsevere disease.
“Rituximab has not been proven as a remission induction in AAV in patients with limited or nonsevere disease, although broad experience in practice suggests it is effective, as would be expected,” he said.
The research was a project of the Immune Tolerance Network, which receives support from the National Institute of Allergy and Infectious Diseases, the Juvenile Diabetes Research Foundation, Genentech, and Biogen Idec.
Treating nonsevere relapse in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis with an increase in glucocorticoids restores remission but only for a short time, results from the Rituximab in AAV trial show.
The findings identify an important subset of patients with ANCA-associated vasculitis (AAV) who are unable to maintain prolonged remission and may require an alternative treatment approach, wrote investigators in the RAVE-ITN (Rituximab in AAV trial–Immune Tolerance Network) Research Group, led by Dr. John Stone of Massachusetts General Hospital, Boston (Arthritis Rheumatol. 2015 [doi:10.002/art.39104]).
The RAVE study is a randomized, double-blind, placebo-controlled trial comparing rituximab followed by placebo to cyclophosphamide followed by azathioprine for remission induction in patients with ANCA-positive granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). The patients all had severe disease.
Patients who experienced nonsevere relapses between 1 and 18 months were treated with an increased dose of prednisone – without a concomitant change in their non-glucocorticoid immunosuppressants – followed by a taper. The authors defined nonsevere relapses as those with the occurrence of any new disease activity, a Birmingham Vasculitis Activity Score for Wegener’s Granulomatosis (BVAS/WG) of 3 or less, and no major BVAS/WG items.
Of the 44 patients with a first nonsevere relapse, 35 (80%) went into remission following an increase in their prednisone dose.
However 70% of these patients went on to experience a second severe or nonsevere relapse within an average of 6 months.
Only 13 patients (30%) were able to maintain disease-free remission until the end of follow-up, and 8 (18%) were able to do so until their last study visit.
Compared with the 71 patients who maintained relapse-free remission over the study period, patients who were unable to maintain prolonged remission were more likely to have GPA, be PR3-ANCA positive, and have relapsing disease at baseline.
All three of those characteristics occurred in 55% of patients, compared with 30% of patients who maintained remission (P = .01), the researchers reported.
“The high rate of second relapses observed in this subgroup of patients suggests a need for a different treatment paradigm than used in the RAVE trial,” the study authors said.
A coauthor of the study, Dr. Robert F. Spiera, director of the Vasculitis and Scleroderma Program at the Hospital for Special Surgery in New York said the findings suggested that upping the ante in terms of the immunosuppressive therapy beyond steroids should be considered.
In many patients, this may mean re-treating or initiating treatment with rituximab (if they had not previously been treated with that agent for induction of remission), he said, noting that the optimal dose was yet to be defined.
Because patients involved in the current study all had severe disease at trial entry, he advised that the temporary control of relapse that was observed with raising the corticosteroid doses may not apply to patients with nonsevere disease.
“Rituximab has not been proven as a remission induction in AAV in patients with limited or nonsevere disease, although broad experience in practice suggests it is effective, as would be expected,” he said.
The research was a project of the Immune Tolerance Network, which receives support from the National Institute of Allergy and Infectious Diseases, the Juvenile Diabetes Research Foundation, Genentech, and Biogen Idec.
Treating nonsevere relapse in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis with an increase in glucocorticoids restores remission but only for a short time, results from the Rituximab in AAV trial show.
The findings identify an important subset of patients with ANCA-associated vasculitis (AAV) who are unable to maintain prolonged remission and may require an alternative treatment approach, wrote investigators in the RAVE-ITN (Rituximab in AAV trial–Immune Tolerance Network) Research Group, led by Dr. John Stone of Massachusetts General Hospital, Boston (Arthritis Rheumatol. 2015 [doi:10.002/art.39104]).
The RAVE study is a randomized, double-blind, placebo-controlled trial comparing rituximab followed by placebo to cyclophosphamide followed by azathioprine for remission induction in patients with ANCA-positive granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). The patients all had severe disease.
Patients who experienced nonsevere relapses between 1 and 18 months were treated with an increased dose of prednisone – without a concomitant change in their non-glucocorticoid immunosuppressants – followed by a taper. The authors defined nonsevere relapses as those with the occurrence of any new disease activity, a Birmingham Vasculitis Activity Score for Wegener’s Granulomatosis (BVAS/WG) of 3 or less, and no major BVAS/WG items.
Of the 44 patients with a first nonsevere relapse, 35 (80%) went into remission following an increase in their prednisone dose.
However 70% of these patients went on to experience a second severe or nonsevere relapse within an average of 6 months.
Only 13 patients (30%) were able to maintain disease-free remission until the end of follow-up, and 8 (18%) were able to do so until their last study visit.
Compared with the 71 patients who maintained relapse-free remission over the study period, patients who were unable to maintain prolonged remission were more likely to have GPA, be PR3-ANCA positive, and have relapsing disease at baseline.
All three of those characteristics occurred in 55% of patients, compared with 30% of patients who maintained remission (P = .01), the researchers reported.
“The high rate of second relapses observed in this subgroup of patients suggests a need for a different treatment paradigm than used in the RAVE trial,” the study authors said.
A coauthor of the study, Dr. Robert F. Spiera, director of the Vasculitis and Scleroderma Program at the Hospital for Special Surgery in New York said the findings suggested that upping the ante in terms of the immunosuppressive therapy beyond steroids should be considered.
In many patients, this may mean re-treating or initiating treatment with rituximab (if they had not previously been treated with that agent for induction of remission), he said, noting that the optimal dose was yet to be defined.
Because patients involved in the current study all had severe disease at trial entry, he advised that the temporary control of relapse that was observed with raising the corticosteroid doses may not apply to patients with nonsevere disease.
“Rituximab has not been proven as a remission induction in AAV in patients with limited or nonsevere disease, although broad experience in practice suggests it is effective, as would be expected,” he said.
The research was a project of the Immune Tolerance Network, which receives support from the National Institute of Allergy and Infectious Diseases, the Juvenile Diabetes Research Foundation, Genentech, and Biogen Idec.
FROM ARTHRITIS & RHEUMATOLOGY
Key clinical point: ANCA-positive patients with severe disease who experience a nonsevere relapse after remission may require immunosuppressive therapy beyond steroids.
Major finding: A total of 70% of patients who experienced a first nonsevere relapse but went into remission following an increase in their prednisone dose still had a second severe or nonsevere relapse within an average of 6 months.
Data source: A total of 44 patients from the RAVE trial who had nonsevere relapse during months 1-18 of the study.
Disclosures: The research was a project of the Immune Tolerance Network, which receives support from the National Institute of Allergy and Infectious Diseases, the Juvenile Diabetes Research Foundation, Genentech, and Biogen Idec.
