PANLAR: Patients with GPA, MPA should use rituximab over cyclophosphamide
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Key takeaways:
- New Pan American League of Associations for Rheumatology recommendations include remission maintenance guidelines.
- When rituximab is not available, cyclophosphamide is preferable to oral glucocorticoids.
Patients with new or relapsing granulomatosis with polyangiitis or microscopic polyangiitis should receive rituximab over cyclophosphamide, according to new recommendations from the Pan American League of Associations for Rheumatology.
“Over the past 30 years, randomized controlled trials have helped to delineate the treatment of ANCA-associated vasculitis, particularly for patients with GPA and MPA,” Sebastián Juan Magri, MD, of the Hospital Italiano de La Plata, in Buenos Aires, and colleagues wrote in The Lancet Rheumatology. “Once highly fatal, ANCA-associated vasculitis has become a chronic disease for most patients with current therapies.
“In addition, the countries of Latin America comprise a region of the globe with substantial health-care disparities, including restricted access to costly medications with proven efficacy in ANCA-associated vasculitis (eg, rituximab, mepolizumab, and avacopan) for a vast portion of the population,” they added. “Furthermore, variability exists in the management of patients with ANCA-associated vasculitis by local physicians. Cyclophosphamide and prolonged glucocorticoids have been the most frequently used treatment options to date, both of which lead to treatment-related toxicities in most cases.”
To develop new guidelines for the treatment of ANCA-associated vasculitis, the Pan American League of Associations for Rheumatology (PANLAR) assembled a team of seven methodologists and 10 rheumatologists with demonstrated experience treating vasculitis. The rheumatologists assisted the larger team with shaping questions that would guide the research effort. Meanwhile, the methodologists conducted a systematic literature review targeting randomized clinical trials, cohort studies, post-hoc analyses and pooled analyses through March 2021.
After completion of the search, the rheumatologists voted on each question for inclusion in the published list of recommendations. To be included in the final list of recommendations, each item needed to receive at least 70% approval from the voting members of the group. The voting occurred over three rounds, where failed recommendations were discussed before being voted upon for a second time.
The recommendations include 13 considerations for the treatment of GPA and MPA, nine recommendations for the treatment of eosinophilic granulomatosis with polyangiitis (EGPA) and one general statement regarding ANCA-associated vasculitis. The recommendations for GPA and MPA include:
- Patients with new or relapsing severe disease should receive intravenous pulse glucocorticoids instead of oral glucocorticoids.
- Patients with newly diagnosed severe disease should begin treatment with rituximab (Rituxan, Genentech) instead of cyclophosphamide.
- Patients with relapsing severe disease should begin treatment with rituximab instead of cyclophosphamide.
- In patients with new or relapsing disease, those who cannot access rituximab should use intravenous cyclophosphamide over oral cyclophosphamide.
- Patients with new or relapsing disease should avoid combination therapy of rituximab and cyclophosphamide.
- Patients with new or relapsing disease should not have plasma exchange added to their remission induction strategy.
- In patients with new or relapsed disease that is not severe, patients should be treated with methotrexate.
- Patients with new or relapsed disease should use reduced cumulative dosing for glucocorticoid therapy.
- Patients with new or relapsed disease should avoid adding intravenous immunoglobulin therapy.
- If patients achieve remission using rituximab or cyclophosphamide, rituximab should be used to maintain remission.
- In patients who achieve remission after induction therapy, azathioprine is recommended over methotrexate, mycophenolate mofetil, or leflunomide.
- In patients who achieve remission after induction therapy, methotrexate is recommended over mycophenolate mofetil or leflunomide.
- Patients who achieved remission following induction therapy should not receive low-dose prednisone.
The recommendations for EGPA are:
- Patients with new or relapsing severe disease should undergo combination therapy with cyclophosphamide or rituximab in addition to glucocorticoids, instead of glucocorticoids alone.
- Patients with new or relapsing, non-severe disease should be treated with non-specific immunosuppressive therapies and glucocorticoids.
- Patients with new or relapsing non-severe disease should avoid cyclophosphamide.
- Patients with new or relapsing, non-severe disease should not receive mepolizumab as a first-line therapy.
- For patients who relapse while receiving glucocorticoids only, immunosuppressive therapy should be given in addition to glucocorticoids.
- Patients who relapse while receiving glucocorticoids and a non-targeted immunosuppressive therapy should switch therapies and consider adding rituximab.
- Patients with disease refractory to treatment should consider having mepolizumab (Nucala, GlaxoSmithKline) added to their therapy regimen.
- Patients with disease refractory to treatment should not receive omalizumab (Xolair; Genentech, Novartis).
- Patients who achieve remission after induction therapy should add a non-targeted immunosuppressive agent.
Lastly, regarding the management of ANCA-associated vasculitis in general, the team stated that there is no established perfect therapy duration, and duration for specific patients should be guided by their individual situations.
“Glucocorticoids have been an integral part of the treatment for ANCA-associated vasculitis for decades,” Magri and colleagues wrote. “However, high-quality evidence is not available to support strong recommendations on the best route of administration or the most appropriate initial dosing for these patients.”
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