Table 2.

Summary table of the CanVasc recommendations and statements.

Recommendation or StatementText of the Recommendation or StatementEvidence Level/strength*
  Statement 1ANCA testing with ELISA and IIF methods should be performed for diagnostic purposes in patients in whom there is clinical suspicion of a systemic small- and/or medium-sized vessel vasculitis.
  Statement 2Tissue biopsy should be considered in cases of suspected AAV to confirm diagnosis.
Classification of disease severity in AAV
  Statement 3Patients with AAV should have the extent and severity of their disease categorized as “severe” at the time of diagnosis and in case of subsequent relapse if they have life- or major organ-threatening manifestations, to allow therapy to be tailored accordingly.
The role of referral centers for vasculitis
  Statement 4Patients with AAV, particularly those with challenging disease, should be managed at or in collaboration with a referral center for vasculitis.
Remission induction for newly diagnosed disease
4.1 Remission induction in severe (organ- and/or life-threatening) newly diagnosed disease
  Recommendation 1We recommend remission induction therapy with a combination of high-dose GC and CYC in patients with severe newly diagnosed GPA, MPA, or EGPA.1B/A
  Recommendation 2We recommend using high-dose GC with RTX as first-line remission induction therapy in patients with severe GPA or MPA in whom CYC is contraindicated or in whom CYC presents an unacceptable risk of infertility.1B/A
  Recommendation 3CYC dose should be adjusted in patients > 60 yrs of age and in those with renal impairment.1B/B
  Statement 5CBC and serum creatinine level must be monitored in patients treated with CYC. In patients with abnormal CBC results, temporary withholding of CYC and subsequent dose adjustments may be necessary depending on the degree of leukopenia.
  Recommendation 4We recommend that the remission induction therapy with CYC, combined with GC, last a minimum of 3 to a maximum of 6 mos. Once remission is achieved, CYC should be stopped and the patient switched to a different maintenance therapy.1B/A
  Recommendation 5We recommend that GC be given in adults at an initial dose of 1 mg/kg/day PRED-equivalent for remission induction purposes. This may be preceded by pulsed methylprednisolone (0.5 g/day to 1 g/day for 1 to 3 days) in patients with life-threatening disease and/or major organ involvement.2A/B
  Recommendation 6Prophylaxis against Pneumocystis jirovecii infection should be given to patients receiving CYC or RTX. This prophylaxis consists, in the absence of allergy, of trimethoprim/sulfamethoxazole compounds (800/160 mg 1 tablet 3 times per week or 400/80 mg daily).3/C
  Recommendation 7There is insufficient evidence to support a recommendation that plasma exchange be used as first-line therapy in any patients with AAV. Plasma exchange may be a reasonable adjuvant therapy for patients who clinically deteriorate because of active vasculitis despite ongoing remission induction therapy with high-dose GC and CYC or RTX.4/D
4.2 Remission induction for limited or nonsevere (nonorgan- and nonlife-threatening) newly diagnosed disease
  Recommendation 8In patients with limited and/or nonsevere GPA that is nonlife-threatening and without any major organ involvement, remission induction regimen with MTX in combination with GC can be used.1B/A
  Recommendation 9Patients with nonsevere EGPA or nonsevere MPA without renal involvement can be treated with GC alone for remission induction. At present, there is no consensus on the use of any immunosuppressant agents in combination with GC in patients with EGPA or MPA that are nonsevere (including those with mononeuritis multiplex).2B/C
Remission maintenance therapy
  Recommendation 10In patients with severe AAV in remission after a combined CYC-GC–based induction treatment, maintenance therapy can be based on AZA or MTX, initially in combination with low-dose GC. LEF or mycophenolate mofetil may be alternative agents in patients not tolerating or with contraindications to AZA and MTX.1B/B
  Recommendation 11In patients with severe AAV in remission after a combined CYC-GC–based induction treatment, maintenance therapy with RTX infusions is an alternative to AZA, especially for those patients with PR3-ANCA–positive GPA.1B/A
  Statement 6To date, there is no definitive evidence to guide decisions for maintenance therapy after remission induction with RTX.
  Statement 7Low-dose GC should be part of the initial remission maintenance therapy after remission is achieved; there is not enough evidence yet to support further recommendation on the optimal duration of low-dose GC.
  Recommendation 12We recommend the use of AZA, MTX, or their alternatives (as per Recommendations 10 and 11) for remission maintenance therapy to be continued for a minimum of 18 mos after successful remission induction. There is not yet enough evidence to support further recommendation on the optimal duration of their use for maintenance.3/C
  Recommendation 13The use of trimethoprim/sulfamethoxazole (800/160 mg twice daily) as remission maintenance therapy can be considered in GPA as an adjuvant to immunosuppressant or after the cessation of maintenance immunosuppressive treatment.3/C
  Recommendation 14Topical therapies may be considered, in combination with the systemic therapy and in collaboration with ENT subspecialists, to alleviate the symptoms of upper airway and ENT disease.3/C
Relapsing disease
  Recommendation 15We recommend remission induction of a major organ- or life-threatening relapse with either CYC or RTX in conjunction with high-dose GC. In patients who already received CYC for initial remission induction or a previous disease flare, we recommend using RTX for remission reinduction.1B/A
  Recommendation 16There is insufficient evidence to support a recommendation that plasma exchange be used as first-line therapy in all patients with relapsing AAV with severe renal (GFR < 50 ml/min) or pulmonary hemorrhage. Plasma exchange may be a reasonable adjuvant therapy for patients who clinically deteriorate because of active relapsing vasculitis despite ongoing remission induction therapy with high-dose GC and CYC or RTX.4/D
  Recommendation 17We recommend that relapses that are nonsevere, i.e., nonlife- and nonorgan-threatening, be treated with an increase in GC dose in addition to optimizing the patient’s concurrent immunosuppressant agent.3/C
Refractory disease
  Recommendation 18We recommend the use of RTX in combination with GC in patients with severe GPA or MPA who fail to respond to CYC as remission induction therapy.3/C
  Statement 8Patients with refractory disease should be managed in a referral center for vasculitis in collaboration with subspecialists with experience in managing such patients.
  Statement 9Patients with EGPA and persistent asthmatic symptoms, despite remission of their vasculitic manifestations, should be managed in collaboration with a physician subspecializing in asthma management.
Additional and experimental therapies
  Statement 10In patients in whom the aforementioned therapies are ineffective, contraindicated, or poorly tolerated, consideration can be given to alternate, additional, and/or experimental therapies in collaboration with a referral center for vasculitis.
Followup of patients with AAV
  Statement 11Patients with AAV should be followed regularly for many yrs with full clinical assessment and routine laboratory work to assess disease course and track for disease activity and disease- or treatment-related damage.
  Statement 12All patients previously treated with CYC should have a urinalysis every 3–6 mos as a lifelong means of screening for CYC-induced bladder toxicity. If micro- or macroscopic hematuria is present, in the absence of an alternate explanation, the patient should be referred for consideration of a cystoscopy.
  Statement 13As part of their lifelong annual followup, CV risk factors (including smoking status, diabetes, hypercholesterolemia, HTN, and obesity) and risk for osteoporosis should be systematically assessed, with treatment as needed according to the current respective guidelines for each of these conditions.
Special patient groups
  Statement 14Women with AAV should not consider pregnancy earlier than 6 mos after sustained remission of their disease has been achieved. Women with AAV planning pregnancy and those pregnant should be managed in close collaboration with an obstetrician with expertise in this field and/or in high-risk pregnancies.
  Statement 15There are no pediatric-specific management guidelines for pediatric AAV yet, and most knowledge in pediatric AAV is adapted from adult research. Management of children with AAV should be provided by pediatric physicians at an academic healthcare center, in collaboration with referral centers for vasculitis and/or centers with special interest in pediatric vasculitis.
  Statement 16AAV in children should be classified at the time of diagnosis based on the childhood EULAR/PRINTO/PReS criteria so that therapy can be tailored accordingly.
  Statement 17Children with newly diagnosed AAV should be treated according to adult recommendations for induction of remission and then maintenance, with medication dose adjusted for this specific population.
  Recommendation 19In children, severe relapsing AAV or severe AAV refractory to the combination of CYC and GC (with major organ involvement or life-threatening manifestations) should be treated with RTX in combination with GC.4/D
  • * Statements are not related to specific treatments and were not graded because there was no strong evidence or available studies to support them.

  • CanVasc: Canadian Vasculitis Research Network; ANCA: antineutrophil cytoplasm antibody; IIF: indirect immunofluorescence; AAV: ANCA-associated vasculitides; GC: glucocorticoids; CYC: cyclophosphamide; GPA: granulomatosis with polyangiitis; MPA: microscopic polyangiitis; EGPA: eosinophilic GPA; RTX: rituximab; CBC: complete blood count; PRED: prednisone; MTX: methotrexate; AZA: azathioprine; PR3: proteinase 3; GFR: glomerular filtration rate; CV: cardiovascular; HTN: hypertension; PRINTO: Paediatric Rheumatology International Trial Organization; PreS: Paediatric Rheumatology European Society; LEF: leflunomide; EULAR: European League Against Rheumatism.