Together with the European Renal Association−European Dialysis and Transplant Association (ERA-EDTA), the European League Against Rheumatism (EULAR) has published updated recommendations for the management of patients with antineutrophil cytoplasmic antibody−associated vasculitis (AAV; Yates M, et al. Ann Rheum Dis. 2016;75:1583-1594). A rare and very flexible disease group that is unpredictable and potentially life-threatening, and for which management expertise has been difficult to maintain, AAV has been the subject of multiple papers and the recipient of an indication for treatment with rituximab between the publication of these updates and the EULAR publication of recommendations for managing primary small- and medium-vessel vasculitis, including management of AAV, in 2009. The updated recommendations focus on reassessing standard therapy for patients with AAV, including the prognostic value of histopathology, management of long-term complications, and use of biologic agents.
Cooperating with EULAR standardized operating procedures, a task force comprising 21 members representing EULAR and ERA-EDTA elaborated, evaluated, disseminated, and implemented the recommendation updates. The task force members included a patient, nurse, pathologist, otorhinolaryngologist, pulmonologist, immunologist, and ophthalmologist, 2 general internists, 6 renal physicians, and 6 rheumatologists, all with academic or clinical experience in the vasculitis field.
New items and those requiring updates were identified through a Delphi exercise, which instructed the strategy for a systematic literature review. The Critical Appraisal Skills Programme checklist was used to formally score manuscripts.
“AAV adversely affects quality of life even in patients thought to have clinical remission,” stated Max Yates, BSC, MBBS, MRCP, MSC, Research Fellow, Department of Rheumatology, Norfolk and Norwich University Hospital, United Kingdom, and colleagues in their report of the recommendations. “This may be an effect of the disease or its treatment. We recommend the overarching principle of shared decision making between the patient and their specialist,” they stated.
Key Points from the Updated Guidelines
- Patients with AAV should be managed at, or in close collaboration with, centers of expertise
- Because a positive biopsy strongly supports a vasculitis diagnosis, biopsies should be used to assist in establishing a new diagnosis, and for further evaluating patients suspected of having relapsing vasculitis
- For patients with new-onset organ-threatening or life-threatening AAV, remission induction should consist of treatment with a combination of glucocorticoids and either cyclophosphamide or rituximab
- For patients with nonorgan-threatening AAV, remission induction should consist of treatment with a combination of glucocorticoids and either methotrexate or mycophenolate mofetil
- Treat patients with a major relapse of organ-threatening or life-threatening disease in AAV with a combination of glucocorticoids and either cyclophosphamide or rituximab
- Consider plasma exchange for patients with AAV who have a serum creatinine level of >500 mmol/L (5.7 mg/dL) because of rapidly progressive glomerulonephritis in new or relapsing disease settings
- Use a combination treatment of low-dose glucocorticoids and either azathioprine, rituximab, methotrexate, or mycophenolate mofetil for remission maintenance of AAV
- After achieving sustained remission, patients should continue with remission-maintenance therapy for ≥24 months
- Patients with AAV refractory to remission-induction therapy should be switched from cyclophosphamide to rituximab, or from rituximab to cyclophosphamide, and referred to, or managed in close conjunction with, an expert center for further evaluation
- Decisions about changes in treatment for patients with AAV should be informed by structured clinical assessment rather than antineutrophil cytoplasmic antibody testing
- Persistent unexplained ematuria should be investigated in patients previously exposed to cyclophosphamide
- Because hypoimmunoglobulinemia has been noted following treatment with rituximab, serum immunoglobulin levels should be tested in patients with recurrent infection before each course of rituximab
- Periodically assess patients with AAV for cardiovascular risk
- Provide patients with AAV with a clear, verbal explanation of the nature of their disease, their treatment options, treatment side effects, and short- and long-term prognoses
- After the remission-induction phase of treatment, assess the extent and ongoing impact of comorbidities associated with a patient’s AAV diagnosis, and advise the patient on where they can find support or therapies for these conditions.
“The previous recommendations were published in 2009 and importantly had a wider remit, covering small and medium vessel vasculitis and not just AAV,” said Mr Yates and colleagues. “Readers are encouraged to refer to them for treatment decisions on: mixed essential cryoglobulinaemic vasculitis (non-viral), the use of antiviral therapy for the treatment of hepatitis C-associated cryoglobulinaemic vasculitis and antiviral therapy, PLEX [plasma exchange] and glucocorticoids for hepatitis B-associated polyarteritis nodosa (PAN).”
“Ultimately the treatment aim of viral-associated cryoglobulinaemic vasculitis should be to treat the underlying viral disease according to current best management strategies,” they added.