Experience Proved Rituximab Best for Vasculitis

NEWPORT BEACH, CALIF. – Rituximab is a good remission induction agent in patients with small vessel vasculitis, such as Wegener’s granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome, according to Dr. Leonard Calabrese, chair of clinical immunology and professor of medicine at the Cleveland Clinic.

It appears to be a better choice in some patients than cyclophosphamide, the traditional option, although cyclophosphamide remains the standard of care for remission induction in patients with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis, he said at Perspectives in Rheumatic Diseases 2012.

The Food and Drug Administration approved rituximab for small vessel vasculitis in 2011 based on a trial that pitted cyclophosphamide induction and azathioprine maintenance against a 6-month regimen of rituximab, with patients in both arms of the study receiving prednisone. They all had severe but not fulminant Wegener’s granulomatosis or microscopic polyangiitis; over half had renal involvement.

Of the 99 rituximab patients, 63 (64%) reached the primary end point of steroid-free remission at 6 months, compared with 52 (53%) of the 98 cyclophosphamide patients. (N. Engl. J. Med. 2010;363:221-32).

At 18 months follow-up, 36% of rituximab patients remained in remission without treatment.

"All the trends in the trial favored rituximab. Patients who came in with [new] disease had equal outcomes. If they had relapsed on [cyclophosphamide], rituximab was significantly better," Dr. Calabrese said.

Given the results, and the fact that rituximab might have fewer long-term side effects, it "is favored as the initial therapy for patients who would otherwise be offered cyclophosphamide. Clearly, rituximab is the drug of choice for [cyclophosphamide] relapsers," he said.

Also based on the results, Dr. Calabrese said he is comfortable stopping therapy and observing patients "with new-onset moderate disease that melts away" with rituximab.

But for patients with a relapsing course or who respond only partially to rituximab, "I don’t favor observation. I think repeated rituximab or an antimetabolite is in order. Most the time, I’ve been doing repeated rituximab," he said.

The optimal rituximab patient remains unclear. "There’s more work to be done on the [study] results. We are looking for predictors," he said.

Meanwhile, "cyclophosphamide and apheresis are still my go-to therapies for patients who are ventilator dependent or have a pulmonary or renal presentation," Dr. Calabrese said.

Azathioprine, methotrexate, leflunomide, and mycophenolate are among the options for step-down therapy when patients are treated traditionally with cyclophosphamide for remission, but findings from a recent study showed "there’s no doubt that azathioprine is more effective than mycophenolate for remission maintenance. Azathioprine, in those who can tolerate it, is quite good," he said (JAMA 2010;304:2381-8).

When patients don’t have life-threatening target organ involvement – no red blood–cell casts in the urine, no hypoxic lung involvement, and normal creatinines and liver functions – methotrexate alone might be the best option.

Such patients "tend to be young and have upper-airway-limited disease. These people are very good methotrexate candidates, 20-25 mg/day with high dose glucocorticoids," he said.

For mild, limited disease, "methotrexate works great," he said.

Dr. Calabrese is a consultant for Aventis, Bristol-Myers Squibb, Genentech, Janssen, and Pfizer. He is a speaker for Amgen. The meeting was held by Global Academy for Medical Education. GAME and this news organization are owned by Frontline Medical Communications.

NEWPORT BEACH, CALIF. – Rituximab is a good remission induction agent in patients with small vessel vasculitis, such as Wegener’s granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome, according to Dr. Leonard Calabrese, chair of clinical immunology and professor of medicine at the Cleveland Clinic.

It appears to be a better choice in some patients than cyclophosphamide, the traditional option, although cyclophosphamide remains the standard of care for remission induction in patients with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis, he said at Perspectives in Rheumatic Diseases 2012.

The Food and Drug Administration approved rituximab for small vessel vasculitis in 2011 based on a trial that pitted cyclophosphamide induction and azathioprine maintenance against a 6-month regimen of rituximab, with patients in both arms of the study receiving prednisone. They all had severe but not fulminant Wegener’s granulomatosis or microscopic polyangiitis; over half had renal involvement.

Of the 99 rituximab patients, 63 (64%) reached the primary end point of steroid-free remission at 6 months, compared with 52 (53%) of the 98 cyclophosphamide patients. (N. Engl. J. Med. 2010;363:221-32).

At 18 months follow-up, 36% of rituximab patients remained in remission without treatment.

"All the trends in the trial favored rituximab. Patients who came in with [new] disease had equal outcomes. If they had relapsed on [cyclophosphamide], rituximab was significantly better," Dr. Calabrese said.

Given the results, and the fact that rituximab might have fewer long-term side effects, it "is favored as the initial therapy for patients who would otherwise be offered cyclophosphamide. Clearly, rituximab is the drug of choice for [cyclophosphamide] relapsers," he said.

Also based on the results, Dr. Calabrese said he is comfortable stopping therapy and observing patients "with new-onset moderate disease that melts away" with rituximab.

But for patients with a relapsing course or who respond only partially to rituximab, "I don’t favor observation. I think repeated rituximab or an antimetabolite is in order. Most the time, I’ve been doing repeated rituximab," he said.

The optimal rituximab patient remains unclear. "There’s more work to be done on the [study] results. We are looking for predictors," he said.

Meanwhile, "cyclophosphamide and apheresis are still my go-to therapies for patients who are ventilator dependent or have a pulmonary or renal presentation," Dr. Calabrese said.

Azathioprine, methotrexate, leflunomide, and mycophenolate are among the options for step-down therapy when patients are treated traditionally with cyclophosphamide for remission, but findings from a recent study showed "there’s no doubt that azathioprine is more effective than mycophenolate for remission maintenance. Azathioprine, in those who can tolerate it, is quite good," he said (JAMA 2010;304:2381-8).

When patients don’t have life-threatening target organ involvement – no red blood–cell casts in the urine, no hypoxic lung involvement, and normal creatinines and liver functions – methotrexate alone might be the best option.

Such patients "tend to be young and have upper-airway-limited disease. These people are very good methotrexate candidates, 20-25 mg/day with high dose glucocorticoids," he said.

For mild, limited disease, "methotrexate works great," he said.

Dr. Calabrese is a consultant for Aventis, Bristol-Myers Squibb, Genentech, Janssen, and Pfizer. He is a speaker for Amgen. The meeting was held by Global Academy for Medical Education. GAME and this news organization are owned by Frontline Medical Communications.

NEWPORT BEACH, CALIF. – Rituximab is a good remission induction agent in patients with small vessel vasculitis, such as Wegener’s granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome, according to Dr. Leonard Calabrese, chair of clinical immunology and professor of medicine at the Cleveland Clinic.

It appears to be a better choice in some patients than cyclophosphamide, the traditional option, although cyclophosphamide remains the standard of care for remission induction in patients with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis, he said at Perspectives in Rheumatic Diseases 2012.

The Food and Drug Administration approved rituximab for small vessel vasculitis in 2011 based on a trial that pitted cyclophosphamide induction and azathioprine maintenance against a 6-month regimen of rituximab, with patients in both arms of the study receiving prednisone. They all had severe but not fulminant Wegener’s granulomatosis or microscopic polyangiitis; over half had renal involvement.

Of the 99 rituximab patients, 63 (64%) reached the primary end point of steroid-free remission at 6 months, compared with 52 (53%) of the 98 cyclophosphamide patients. (N. Engl. J. Med. 2010;363:221-32).

At 18 months follow-up, 36% of rituximab patients remained in remission without treatment.

"All the trends in the trial favored rituximab. Patients who came in with [new] disease had equal outcomes. If they had relapsed on [cyclophosphamide], rituximab was significantly better," Dr. Calabrese said.

Given the results, and the fact that rituximab might have fewer long-term side effects, it "is favored as the initial therapy for patients who would otherwise be offered cyclophosphamide. Clearly, rituximab is the drug of choice for [cyclophosphamide] relapsers," he said.

Also based on the results, Dr. Calabrese said he is comfortable stopping therapy and observing patients "with new-onset moderate disease that melts away" with rituximab.

But for patients with a relapsing course or who respond only partially to rituximab, "I don’t favor observation. I think repeated rituximab or an antimetabolite is in order. Most the time, I’ve been doing repeated rituximab," he said.

The optimal rituximab patient remains unclear. "There’s more work to be done on the [study] results. We are looking for predictors," he said.

Meanwhile, "cyclophosphamide and apheresis are still my go-to therapies for patients who are ventilator dependent or have a pulmonary or renal presentation," Dr. Calabrese said.

Azathioprine, methotrexate, leflunomide, and mycophenolate are among the options for step-down therapy when patients are treated traditionally with cyclophosphamide for remission, but findings from a recent study showed "there’s no doubt that azathioprine is more effective than mycophenolate for remission maintenance. Azathioprine, in those who can tolerate it, is quite good," he said (JAMA 2010;304:2381-8).

When patients don’t have life-threatening target organ involvement – no red blood–cell casts in the urine, no hypoxic lung involvement, and normal creatinines and liver functions – methotrexate alone might be the best option.

Such patients "tend to be young and have upper-airway-limited disease. These people are very good methotrexate candidates, 20-25 mg/day with high dose glucocorticoids," he said.

For mild, limited disease, "methotrexate works great," he said.

Dr. Calabrese is a consultant for Aventis, Bristol-Myers Squibb, Genentech, Janssen, and Pfizer. He is a speaker for Amgen. The meeting was held by Global Academy for Medical Education. GAME and this news organization are owned by Frontline Medical Communications.