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04-16-2015, 11:11 AM
Relapse Common in ANCA VasculitisJust increasing the steroid dose was inadequate in many patients.by Nancy Walsh ([email protected])
Senior Staff Writer, MedPage Today
Action Points
Relapses are common in ANCA-associated vasculitis after initial disease remission, with non-severe relapses more common than severe ones.
Steroid-induced remissions of non-severe disease relapses are highly likely, but infrequently sustained.
Most patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis who experienced non-severe relapses after immunosuppressive induction therapy were able to achieve only temporary remission with an increase in glucocorticoid dose, analysis of data from a double-blind study found.
Among 44 patients who had a non-severe relapse during 18 months of follow-up, 80% reached remission after an increase in prednisone dose to a median of 17.5 mg/day (range 2.5 to 80), according to John H. Stone, MD (http://www.massgeneral.org/doctors/doctor.aspx?id=17672), director of clinical rheumatology at Massachusetts General Hospital in Boston, and colleagues.
However, in only 30% was remission maintained through the 18-month follow-up. The mean time to the second relapse was 9.4 months, and in almost half the relapses were considered severe, the researchers reported online in Arthritis and Rheumatology (http://onlinelibrary.wiley.com/journal/10.1002/%28ISSN%292326-5205/accepted).
The primary types of ANCA-associated vasculitides are granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis) and microscopic polyangiitis. The usual treatment of these conditions consists of induction therapy with cyclophosphamide, rituximab (Rituxan), or methotrexate, but during long-term follow-up more than half of patients relapse.
"Despite reports from some clinical trials (http://www.ncbi.nlm.nih.gov/pubmed/15673801) that non-severe relapses are three times more common than severe relapses, the clinical course, treatment outcomes, and ultimate implications of such disease relapses remain largely unexamined," Stone and colleagues wrote.
Non-severe relapses are those that "do not pose immediate threats either to major organ function or the patient's life," they noted.
To address this gap, they analyzed data from the published Rituximab in ANCA-Associated Vasculitis trial (RAVE) (http://www.ncbi.nlm.nih.gov/pubmed/20647199), in which patients with severe disease were treated with cyclophosphamide for 3 to 6 months and then given maintenance therapy with azathioprine through month 18, or were treated with four weekly infusions of rituximab followed by azathioprine or placebo. All patients received prednisone, intended to be tapered and stopped by 6 months.
For inclusion in the trial, patients had to have a Birmingham Vasculitis Activity Score (BVAS) of 3 or one major disease manifestation such as alveolar hemorrhage or serious renal disease. Remission was a BVAS of 0, and non-severe relapse was defined as an increase in BVAS of no more than 3 and no major disease manifestations. Severe relapse was a return to vasculitis activity necessitating cyclophosphamide plus high-dose steroid treatment.
Non-severe relapses were treated with an increase in prednisone dose determined by the investigator for a month, followed by tapering.
During the 18 months of follow-up, 44 patients had non-severe relapses, 41 patients had severe relapses, and 71 remained relapse-free. The average time until first relapse was 7.5 months.
Among patients who had non-severe relapses, 91% had granulomatosis with polyangiitis, 82% had the PR3 subtype of ANCA, and 64% had a history of relapsing disease at baseline.
More than half (55%) of patients with non-severe relapses had all three of those disease features, compared with 30% of those who remained in remission.
The most common manifestations of non-severe relapse were lung, eye, ear, and nose involvement.
The outcome following relapse did not appear to differ depending on whether high- or low-dose prednisone was used. For those who received 20 mg/day or more, 77% once again reached remission and 23% stayed in remission until the study conclusion, while the numbers for those given less than 20 mg/day were 82% and 36%.
A total of 36% of patients given high-dose prednisone had another non-severe relapse, as did 41% of those on the lower dose, while 41% of patients on the high dose had a severe relapse as did 23% of those on the low dose.
"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," Stone and colleagues observed.
One possibility could be B-cell depletion with rituximab rather than maintenance with azathioprine. In a recent clinical trial (http://www.ncbi.nlm.nih.gov/pubmed/?term=guillevin+l+i+pagnoux+c+karras+a+rituximab+a zathioprine+anca) comparing these two agents for maintenance therapy in ANCA-associated vasculitis, more patients receiving rituximab remained in remission at 28 months.
The practice of continuing prednisone for long periods in these patients continues to be controversial.
"Although the follow-up period in this study was likely too short to detect differences in treatment-related adverse events or damage, a recent study of patients with rheumatoid arthritis demonstrated that treatment with prednisone 8 mg/day or higher was associated with an increase in death from any cause in a dose-dependent manner, suggesting that the long-term effects of chronic glucocorticoid use in doses required to maintain stability in granulomatosis with polyangiitis may be substantial," the researchers cautioned.
An ongoing study known as The Assessment of Prednisone In Remission (TAPIR) (https://clinicaltrials.gov/ct2/show/NCT01933724?term=prednisone+remission+tapir&rank=1) may help clarify the role of low-dose prednisone in these vasculitides.
A limitation of this study was the lack of standardization of prednisone doses.
Link:
Relapse Common in ANCA Vasculitis | Medpage Today (http://www.medpagetoday.com/Rheumatology/GeneralRheumatology/50545)
Senior Staff Writer, MedPage Today
Action Points
Relapses are common in ANCA-associated vasculitis after initial disease remission, with non-severe relapses more common than severe ones.
Steroid-induced remissions of non-severe disease relapses are highly likely, but infrequently sustained.
Most patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis who experienced non-severe relapses after immunosuppressive induction therapy were able to achieve only temporary remission with an increase in glucocorticoid dose, analysis of data from a double-blind study found.
Among 44 patients who had a non-severe relapse during 18 months of follow-up, 80% reached remission after an increase in prednisone dose to a median of 17.5 mg/day (range 2.5 to 80), according to John H. Stone, MD (http://www.massgeneral.org/doctors/doctor.aspx?id=17672), director of clinical rheumatology at Massachusetts General Hospital in Boston, and colleagues.
However, in only 30% was remission maintained through the 18-month follow-up. The mean time to the second relapse was 9.4 months, and in almost half the relapses were considered severe, the researchers reported online in Arthritis and Rheumatology (http://onlinelibrary.wiley.com/journal/10.1002/%28ISSN%292326-5205/accepted).
The primary types of ANCA-associated vasculitides are granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis) and microscopic polyangiitis. The usual treatment of these conditions consists of induction therapy with cyclophosphamide, rituximab (Rituxan), or methotrexate, but during long-term follow-up more than half of patients relapse.
"Despite reports from some clinical trials (http://www.ncbi.nlm.nih.gov/pubmed/15673801) that non-severe relapses are three times more common than severe relapses, the clinical course, treatment outcomes, and ultimate implications of such disease relapses remain largely unexamined," Stone and colleagues wrote.
Non-severe relapses are those that "do not pose immediate threats either to major organ function or the patient's life," they noted.
To address this gap, they analyzed data from the published Rituximab in ANCA-Associated Vasculitis trial (RAVE) (http://www.ncbi.nlm.nih.gov/pubmed/20647199), in which patients with severe disease were treated with cyclophosphamide for 3 to 6 months and then given maintenance therapy with azathioprine through month 18, or were treated with four weekly infusions of rituximab followed by azathioprine or placebo. All patients received prednisone, intended to be tapered and stopped by 6 months.
For inclusion in the trial, patients had to have a Birmingham Vasculitis Activity Score (BVAS) of 3 or one major disease manifestation such as alveolar hemorrhage or serious renal disease. Remission was a BVAS of 0, and non-severe relapse was defined as an increase in BVAS of no more than 3 and no major disease manifestations. Severe relapse was a return to vasculitis activity necessitating cyclophosphamide plus high-dose steroid treatment.
Non-severe relapses were treated with an increase in prednisone dose determined by the investigator for a month, followed by tapering.
During the 18 months of follow-up, 44 patients had non-severe relapses, 41 patients had severe relapses, and 71 remained relapse-free. The average time until first relapse was 7.5 months.
Among patients who had non-severe relapses, 91% had granulomatosis with polyangiitis, 82% had the PR3 subtype of ANCA, and 64% had a history of relapsing disease at baseline.
More than half (55%) of patients with non-severe relapses had all three of those disease features, compared with 30% of those who remained in remission.
The most common manifestations of non-severe relapse were lung, eye, ear, and nose involvement.
The outcome following relapse did not appear to differ depending on whether high- or low-dose prednisone was used. For those who received 20 mg/day or more, 77% once again reached remission and 23% stayed in remission until the study conclusion, while the numbers for those given less than 20 mg/day were 82% and 36%.
A total of 36% of patients given high-dose prednisone had another non-severe relapse, as did 41% of those on the lower dose, while 41% of patients on the high dose had a severe relapse as did 23% of those on the low dose.
"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," Stone and colleagues observed.
One possibility could be B-cell depletion with rituximab rather than maintenance with azathioprine. In a recent clinical trial (http://www.ncbi.nlm.nih.gov/pubmed/?term=guillevin+l+i+pagnoux+c+karras+a+rituximab+a zathioprine+anca) comparing these two agents for maintenance therapy in ANCA-associated vasculitis, more patients receiving rituximab remained in remission at 28 months.
The practice of continuing prednisone for long periods in these patients continues to be controversial.
"Although the follow-up period in this study was likely too short to detect differences in treatment-related adverse events or damage, a recent study of patients with rheumatoid arthritis demonstrated that treatment with prednisone 8 mg/day or higher was associated with an increase in death from any cause in a dose-dependent manner, suggesting that the long-term effects of chronic glucocorticoid use in doses required to maintain stability in granulomatosis with polyangiitis may be substantial," the researchers cautioned.
An ongoing study known as The Assessment of Prednisone In Remission (TAPIR) (https://clinicaltrials.gov/ct2/show/NCT01933724?term=prednisone+remission+tapir&rank=1) may help clarify the role of low-dose prednisone in these vasculitides.
A limitation of this study was the lack of standardization of prednisone doses.
Link:
Relapse Common in ANCA Vasculitis | Medpage Today (http://www.medpagetoday.com/Rheumatology/GeneralRheumatology/50545)