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– Cleveland Clinic rheumatologist Alexandra Villa-Forte, MD, MPH, has a vivid way of describing the challenge of maintaining remission in granulomatosis with polyangiitis (GPA): She called it “the worst nightmare in the clinic” in a presentation at the annual Perspectives in Rheumatic Diseases.

Dr. Villa-Forte should know. She’s treated more than 700 patients with GPA, also known as Wegener’s granulomatosis, a rare disorder that causes necrotizing vasculitis of small arteries and veins. She advises close monitoring of patients in remission, caution regarding toxicity, pneumonia prophylaxis, and an understanding of the limitations of existing medications.

An estimated 3 in 100,000 people have GPA, which can be fatal if it’s not treated. “All patients with active GPA should receive prednisone with a second agent,” she said at the conference, held by Global Academy for Medical Education. “We know that increasing the prednisone or using it alone will not result in sustained remission at all.”

According to her, new concepts in therapeutic guidance suggest four criteria should determine the specific agents used: Involvement of critical organ systems, severity of clinical manifestations, rate of change (such as rapidly progressing kidney failure), and individual patient factors such as comorbidities.

Patients facing immediate risk to life or organ function should get higher doses of corticosteroids, a cytotoxic agent, and perhaps plasmapheresis, she said.

Induction therapy should last 3-6 months, followed by maintenance therapy that keeps the condition at bay, Dr. Villa-Forte said. But things do not always go according to plan.

“The main challenge that we encounter is that relapses still occur during treatment. The patient could be on appropriate treatment and appropriate doses and they still relapse,” she said. “The second challenge is that patients who come off treatment have a very high rate of relapse.”

Research suggests that up to 70% of patients off medication relapse by 18 months, and 15%-35% of patients on medication relapse by 12-18 months, Dr. Villa-Forte said.

“Every time a patient relapses, it means induction therapy and high doses of prednisone are started all over again,” she said. “Multiple relapses are associated with a very high rate of complications. That’s what we’re trying to avoid through successful maintenance therapy.”

Which agent is best for maintenance? Research has suggested that there’s little difference in relapse rates between methotrexate and azathioprine, while mycophenolate mofetil was linked to more relapses than was azathioprine. Other research has found that rituximab (Rituxan) is superior to azathioprine at sustaining remission and overall survival (N Engl J Med. 2014 Nov 6;371[19]:1771-80).

Questions about rituximab remain, Dr. Villa-Forte said: Can remission be sustained with fewer infusions? Would higher doses produce long-term benefit after therapy is halted without boosting toxicity?

Regardless of the drug used, relapses from remission are still frequent, suggesting the need to focus on special treatment for patients at higher risk for relapse, she said.

For now, she gave these tips about how to treat patients in remission:

• Reduce treatment toxicity (it’s “significant over time and not better with rituximab”) and focus on disease activity and complications.

• Take regular labs and get a fresh urine sediment analysis with every visit. In some cases, the urine analysis in patients who seem healthy will reveal hematuria, a sign of nephritis. Then, “you have to make a decision about changing the treatment just by looking at the urine.”

• Pay attention to the risk of thrombosis.

• Put patients on Pneumocystis carinii pneumonia prophylaxis even if they’re only on a bit of prednisone.

• Be aware of risk factors for relapse, including a history of at least one relapse and stopping therapy before 48 months.

Dr. Villa-Forte had no relevant disclosures.

Global Academy for Medical Education and this news organization are owned by the same parent company.

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– Cleveland Clinic rheumatologist Alexandra Villa-Forte, MD, MPH, has a vivid way of describing the challenge of maintaining remission in granulomatosis with polyangiitis (GPA): She called it “the worst nightmare in the clinic” in a presentation at the annual Perspectives in Rheumatic Diseases.

Dr. Villa-Forte should know. She’s treated more than 700 patients with GPA, also known as Wegener’s granulomatosis, a rare disorder that causes necrotizing vasculitis of small arteries and veins. She advises close monitoring of patients in remission, caution regarding toxicity, pneumonia prophylaxis, and an understanding of the limitations of existing medications.

An estimated 3 in 100,000 people have GPA, which can be fatal if it’s not treated. “All patients with active GPA should receive prednisone with a second agent,” she said at the conference, held by Global Academy for Medical Education. “We know that increasing the prednisone or using it alone will not result in sustained remission at all.”

According to her, new concepts in therapeutic guidance suggest four criteria should determine the specific agents used: Involvement of critical organ systems, severity of clinical manifestations, rate of change (such as rapidly progressing kidney failure), and individual patient factors such as comorbidities.

Patients facing immediate risk to life or organ function should get higher doses of corticosteroids, a cytotoxic agent, and perhaps plasmapheresis, she said.

Induction therapy should last 3-6 months, followed by maintenance therapy that keeps the condition at bay, Dr. Villa-Forte said. But things do not always go according to plan.

“The main challenge that we encounter is that relapses still occur during treatment. The patient could be on appropriate treatment and appropriate doses and they still relapse,” she said. “The second challenge is that patients who come off treatment have a very high rate of relapse.”

Research suggests that up to 70% of patients off medication relapse by 18 months, and 15%-35% of patients on medication relapse by 12-18 months, Dr. Villa-Forte said.

“Every time a patient relapses, it means induction therapy and high doses of prednisone are started all over again,” she said. “Multiple relapses are associated with a very high rate of complications. That’s what we’re trying to avoid through successful maintenance therapy.”

Which agent is best for maintenance? Research has suggested that there’s little difference in relapse rates between methotrexate and azathioprine, while mycophenolate mofetil was linked to more relapses than was azathioprine. Other research has found that rituximab (Rituxan) is superior to azathioprine at sustaining remission and overall survival (N Engl J Med. 2014 Nov 6;371[19]:1771-80).

Questions about rituximab remain, Dr. Villa-Forte said: Can remission be sustained with fewer infusions? Would higher doses produce long-term benefit after therapy is halted without boosting toxicity?

Regardless of the drug used, relapses from remission are still frequent, suggesting the need to focus on special treatment for patients at higher risk for relapse, she said.

For now, she gave these tips about how to treat patients in remission:

• Reduce treatment toxicity (it’s “significant over time and not better with rituximab”) and focus on disease activity and complications.

• Take regular labs and get a fresh urine sediment analysis with every visit. In some cases, the urine analysis in patients who seem healthy will reveal hematuria, a sign of nephritis. Then, “you have to make a decision about changing the treatment just by looking at the urine.”

• Pay attention to the risk of thrombosis.

• Put patients on Pneumocystis carinii pneumonia prophylaxis even if they’re only on a bit of prednisone.

• Be aware of risk factors for relapse, including a history of at least one relapse and stopping therapy before 48 months.

Dr. Villa-Forte had no relevant disclosures.

Global Academy for Medical Education and this news organization are owned by the same parent company.

– Cleveland Clinic rheumatologist Alexandra Villa-Forte, MD, MPH, has a vivid way of describing the challenge of maintaining remission in granulomatosis with polyangiitis (GPA): She called it “the worst nightmare in the clinic” in a presentation at the annual Perspectives in Rheumatic Diseases.

Dr. Villa-Forte should know. She’s treated more than 700 patients with GPA, also known as Wegener’s granulomatosis, a rare disorder that causes necrotizing vasculitis of small arteries and veins. She advises close monitoring of patients in remission, caution regarding toxicity, pneumonia prophylaxis, and an understanding of the limitations of existing medications.

An estimated 3 in 100,000 people have GPA, which can be fatal if it’s not treated. “All patients with active GPA should receive prednisone with a second agent,” she said at the conference, held by Global Academy for Medical Education. “We know that increasing the prednisone or using it alone will not result in sustained remission at all.”

According to her, new concepts in therapeutic guidance suggest four criteria should determine the specific agents used: Involvement of critical organ systems, severity of clinical manifestations, rate of change (such as rapidly progressing kidney failure), and individual patient factors such as comorbidities.

Patients facing immediate risk to life or organ function should get higher doses of corticosteroids, a cytotoxic agent, and perhaps plasmapheresis, she said.

Induction therapy should last 3-6 months, followed by maintenance therapy that keeps the condition at bay, Dr. Villa-Forte said. But things do not always go according to plan.

“The main challenge that we encounter is that relapses still occur during treatment. The patient could be on appropriate treatment and appropriate doses and they still relapse,” she said. “The second challenge is that patients who come off treatment have a very high rate of relapse.”

Research suggests that up to 70% of patients off medication relapse by 18 months, and 15%-35% of patients on medication relapse by 12-18 months, Dr. Villa-Forte said.

“Every time a patient relapses, it means induction therapy and high doses of prednisone are started all over again,” she said. “Multiple relapses are associated with a very high rate of complications. That’s what we’re trying to avoid through successful maintenance therapy.”

Which agent is best for maintenance? Research has suggested that there’s little difference in relapse rates between methotrexate and azathioprine, while mycophenolate mofetil was linked to more relapses than was azathioprine. Other research has found that rituximab (Rituxan) is superior to azathioprine at sustaining remission and overall survival (N Engl J Med. 2014 Nov 6;371[19]:1771-80).

Questions about rituximab remain, Dr. Villa-Forte said: Can remission be sustained with fewer infusions? Would higher doses produce long-term benefit after therapy is halted without boosting toxicity?

Regardless of the drug used, relapses from remission are still frequent, suggesting the need to focus on special treatment for patients at higher risk for relapse, she said.

For now, she gave these tips about how to treat patients in remission:

• Reduce treatment toxicity (it’s “significant over time and not better with rituximab”) and focus on disease activity and complications.

• Take regular labs and get a fresh urine sediment analysis with every visit. In some cases, the urine analysis in patients who seem healthy will reveal hematuria, a sign of nephritis. Then, “you have to make a decision about changing the treatment just by looking at the urine.”

• Pay attention to the risk of thrombosis.

• Put patients on Pneumocystis carinii pneumonia prophylaxis even if they’re only on a bit of prednisone.

• Be aware of risk factors for relapse, including a history of at least one relapse and stopping therapy before 48 months.

Dr. Villa-Forte had no relevant disclosures.

Global Academy for Medical Education and this news organization are owned by the same parent company.

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