Don't Taper Glucocorticoids Too Early in Vasculitis

NEW YORK – Early discontinuation of glucocorticoid therapy may greatly increase the risk of relapse in antineutrophil cytoplasmic antibody–associated vasculitis, Dr. Yusuf Yazici said at a rheumatology meeting sponsored by New York University.

He discussed a study that addressed the controversial question of whether low-dose glucocorticoids contribute to maintaining remission of the disease.

Patients successfully treated for antineutrophil cytoplasmic antibody–associated vasculitis (AAV) face high rates of relapse, up to 38% at 30 months. Although glucocorticoids are often used to prevent relapse in AAV, high-quality evidence to guide treatment is lacking, Dr. Yazici said during an update on the treatment of vasculitis.

"Our aim is always to get patients off steroid therapy, but maybe that is a misguided aim," said Dr. Yazici, director of the Seligman Center for Advanced Therapeutics and Behçet’s Syndrome Evaluation, Treatment and Research Center at the New York University Hospital for Joint Diseases.

Dr. Yazici cited findings from a meta-analysis of studies investigating the treatment of AAV that included a predefined glucocorticoid dose and protocol for tapering (Arthritis Care Res. 2010;62:1166-73). Thirteen studies involving 983 patients were identified for inclusion, including five observational and eight randomized controlled trials. None of the studies directly compared glucocorticoid regimens.

To elucidate the role of glucocorticoid therapy in relapse, the authors divided the studies into those that had a zero glucocorticoid target dose (i.e., aimed to get patients completely off glucocorticoid therapy, n = 695) and those having a nonzero glucocorticoid target dose (i.e., low glucocorticoid maintenance dose allowed, n = 288).

The investigators found that 36% of the overall group relapsed. Upon further examination, the relapse rate was 43% for those in the zero glucocorticoid target dose group, compared with 14% in those allowed to continue glucocorticoids – approximately a threefold increase.

Even for those who discontinue glucocorticoids, timing is important. When the investigators divided patients in the zero target dose into those who had to reach zero within 12 months (the early zero group) and those who were allowed to reach zero after 12 months (the late zero group), there was a 48% relapse rate for the early zero group, compared with a 29% rate for the late zero group. While the early zero glucocorticoid target dose group had significantly more relapses than the nonzero group (P less than .001), the late zero glucocorticoid target dose group was similar to the nonzero group. By grouping the late zero and nonzero groups, the authors concluded that early discontinuation of glucocorticoid was associated with a 20% increased risk of relapse (28% vs. 48%).

This study has several significant messages, said Dr. Yazici. "Small differences in [glucocorticoid] management may have a major impact on relapse rates. It may not be a bad thing to keep AAV patients on steroids a little longer. This is the first study that has looked into this," he noted.

The results suggest that glucocorticoid dose should be monitored, and that patients with AAV should be kept on 5.0-7.5 mg of glucocorticoids for at least a year after reaching disease remission. For clinical trials, failure to consider concomitant glucocorticoid dosing can affect outcomes, especially remission and relapse, as well as sample size determination, said Dr. Yazici.

Dr. Yazici has served as a consultant or speaker for, or has received research support from, BMS, Celgene, Centocor, Genentech, Merck, Novartis, Roche, and UCB.

NEW YORK – Early discontinuation of glucocorticoid therapy may greatly increase the risk of relapse in antineutrophil cytoplasmic antibody–associated vasculitis, Dr. Yusuf Yazici said at a rheumatology meeting sponsored by New York University.

He discussed a study that addressed the controversial question of whether low-dose glucocorticoids contribute to maintaining remission of the disease.

Patients successfully treated for antineutrophil cytoplasmic antibody–associated vasculitis (AAV) face high rates of relapse, up to 38% at 30 months. Although glucocorticoids are often used to prevent relapse in AAV, high-quality evidence to guide treatment is lacking, Dr. Yazici said during an update on the treatment of vasculitis.

"Our aim is always to get patients off steroid therapy, but maybe that is a misguided aim," said Dr. Yazici, director of the Seligman Center for Advanced Therapeutics and Behçet’s Syndrome Evaluation, Treatment and Research Center at the New York University Hospital for Joint Diseases.

Dr. Yazici cited findings from a meta-analysis of studies investigating the treatment of AAV that included a predefined glucocorticoid dose and protocol for tapering (Arthritis Care Res. 2010;62:1166-73). Thirteen studies involving 983 patients were identified for inclusion, including five observational and eight randomized controlled trials. None of the studies directly compared glucocorticoid regimens.

To elucidate the role of glucocorticoid therapy in relapse, the authors divided the studies into those that had a zero glucocorticoid target dose (i.e., aimed to get patients completely off glucocorticoid therapy, n = 695) and those having a nonzero glucocorticoid target dose (i.e., low glucocorticoid maintenance dose allowed, n = 288).

The investigators found that 36% of the overall group relapsed. Upon further examination, the relapse rate was 43% for those in the zero glucocorticoid target dose group, compared with 14% in those allowed to continue glucocorticoids – approximately a threefold increase.

Even for those who discontinue glucocorticoids, timing is important. When the investigators divided patients in the zero target dose into those who had to reach zero within 12 months (the early zero group) and those who were allowed to reach zero after 12 months (the late zero group), there was a 48% relapse rate for the early zero group, compared with a 29% rate for the late zero group. While the early zero glucocorticoid target dose group had significantly more relapses than the nonzero group (P less than .001), the late zero glucocorticoid target dose group was similar to the nonzero group. By grouping the late zero and nonzero groups, the authors concluded that early discontinuation of glucocorticoid was associated with a 20% increased risk of relapse (28% vs. 48%).

This study has several significant messages, said Dr. Yazici. "Small differences in [glucocorticoid] management may have a major impact on relapse rates. It may not be a bad thing to keep AAV patients on steroids a little longer. This is the first study that has looked into this," he noted.

The results suggest that glucocorticoid dose should be monitored, and that patients with AAV should be kept on 5.0-7.5 mg of glucocorticoids for at least a year after reaching disease remission. For clinical trials, failure to consider concomitant glucocorticoid dosing can affect outcomes, especially remission and relapse, as well as sample size determination, said Dr. Yazici.

Dr. Yazici has served as a consultant or speaker for, or has received research support from, BMS, Celgene, Centocor, Genentech, Merck, Novartis, Roche, and UCB.

NEW YORK – Early discontinuation of glucocorticoid therapy may greatly increase the risk of relapse in antineutrophil cytoplasmic antibody–associated vasculitis, Dr. Yusuf Yazici said at a rheumatology meeting sponsored by New York University.

He discussed a study that addressed the controversial question of whether low-dose glucocorticoids contribute to maintaining remission of the disease.

Patients successfully treated for antineutrophil cytoplasmic antibody–associated vasculitis (AAV) face high rates of relapse, up to 38% at 30 months. Although glucocorticoids are often used to prevent relapse in AAV, high-quality evidence to guide treatment is lacking, Dr. Yazici said during an update on the treatment of vasculitis.

"Our aim is always to get patients off steroid therapy, but maybe that is a misguided aim," said Dr. Yazici, director of the Seligman Center for Advanced Therapeutics and Behçet’s Syndrome Evaluation, Treatment and Research Center at the New York University Hospital for Joint Diseases.

Dr. Yazici cited findings from a meta-analysis of studies investigating the treatment of AAV that included a predefined glucocorticoid dose and protocol for tapering (Arthritis Care Res. 2010;62:1166-73). Thirteen studies involving 983 patients were identified for inclusion, including five observational and eight randomized controlled trials. None of the studies directly compared glucocorticoid regimens.

To elucidate the role of glucocorticoid therapy in relapse, the authors divided the studies into those that had a zero glucocorticoid target dose (i.e., aimed to get patients completely off glucocorticoid therapy, n = 695) and those having a nonzero glucocorticoid target dose (i.e., low glucocorticoid maintenance dose allowed, n = 288).

The investigators found that 36% of the overall group relapsed. Upon further examination, the relapse rate was 43% for those in the zero glucocorticoid target dose group, compared with 14% in those allowed to continue glucocorticoids – approximately a threefold increase.

Even for those who discontinue glucocorticoids, timing is important. When the investigators divided patients in the zero target dose into those who had to reach zero within 12 months (the early zero group) and those who were allowed to reach zero after 12 months (the late zero group), there was a 48% relapse rate for the early zero group, compared with a 29% rate for the late zero group. While the early zero glucocorticoid target dose group had significantly more relapses than the nonzero group (P less than .001), the late zero glucocorticoid target dose group was similar to the nonzero group. By grouping the late zero and nonzero groups, the authors concluded that early discontinuation of glucocorticoid was associated with a 20% increased risk of relapse (28% vs. 48%).

This study has several significant messages, said Dr. Yazici. "Small differences in [glucocorticoid] management may have a major impact on relapse rates. It may not be a bad thing to keep AAV patients on steroids a little longer. This is the first study that has looked into this," he noted.

The results suggest that glucocorticoid dose should be monitored, and that patients with AAV should be kept on 5.0-7.5 mg of glucocorticoids for at least a year after reaching disease remission. For clinical trials, failure to consider concomitant glucocorticoid dosing can affect outcomes, especially remission and relapse, as well as sample size determination, said Dr. Yazici.

Dr. Yazici has served as a consultant or speaker for, or has received research support from, BMS, Celgene, Centocor, Genentech, Merck, Novartis, Roche, and UCB.