Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

non-HBV-related PAN

1st line – oral prednisolone + disease-modifying antirheumatic drug (DMARD)

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ACUTE
|
non-HBV-related PAN
|
poor prognosis (5-factor score ≥1)
1st line – 

oral prednisolone + disease-modifying antirheumatic drug (DMARD)

Oral corticosteroids are given in a reducing regimen, eventually tapering to a dose of 15 mg/day over 2 months, followed by a slow reduction with the aim of ceasing treatment to 0 by 15 to 18 months. It may be possible to taper the corticosteroid dose more rapidly in patients 65 years old or older. One study found similar remission rates but less toxicity in this patient population with rapid corticosteroid dose tapering (approximately 9 months) versus conventional treatment with longer corticosteroid duration.[85]

If remission is not achieved with intravenous cyclophosphamide in 3 to 6 months, consider switching to oral cyclophosphamide until remission is achieved. The maximum duration of cyclophosphamide therapy is 6 months. When patients have achieved remission, cyclophosphamide is withdrawn and replaced by an alternative immunosuppressant with continued tapering of corticosteroids.

Maintenance of remission with azathioprine, leflunomide, or methotrexate has been shown to be effective in patients with anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis, and it has been suggested that this could be a potential option for polyarteritis nodosa (PAN).[59]​[64][65][66][67]​​

Primary options

prednisolone: 1 mg/kg/day orally initially, reduce dose gradually to 15 mg/day by 2 months, and cease by 15-18 months

-- AND --

cyclophosphamide: 15 mg/kg intravenously once every 2 weeks for 3 doses, then once every 3 weeks until remission, maximum 1200 mg/dose; or 2 mg/kg/day orally

-- AND --

azathioprine: 2 mg/kg/day orally starting after cyclophosphamide has been ceased

or

leflunomide: 20-30 mg orally once daily starting after cyclophosphamide has been ceased

or

methotrexate: 7.5 to 15 mg orally once weekly on the same day each week initially starting after cyclophosphamide has been ceased, increase by 2.5 mg/week increments every 2-4 weeks according to response, maximum 25 mg/week

Consider – intravenous methylprednisolone

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ACUTE
|
non-HBV-related PAN
|
poor prognosis (5-factor score ≥1)
Consider – 

intravenous methylprednisolone

Additional treatment recommended for SOME patients in selected patient group

Intravenous pulses of methylprednisolone can be given before each infusion of intravenous cyclophosphamide, which may allow a faster tapering of oral corticosteroid.

Primary options

methylprednisolone: 10 mg/kg intravenously before cyclophosphamide infusions, maximum 1000 mg/dose

1st line – oral prednisolone

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ACUTE
|
non-HBV-related PAN
|
good prognosis (5-factor score of 0)
1st line – 

oral prednisolone

Oral corticosteroids are given in a reducing regimen, aiming at 15 mg/day by 2 months, followed by a slow reduction to 0 by 15 to 18 months.

Primary options

prednisolone: 1 mg/kg/day orally initially, reduce dose gradually to 15 mg/day by 2 months, and cease by 15-18 months

Consider – disease-modifying antirheumatic drug (DMARD)

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ACUTE
|
non-HBV-related PAN
|
good prognosis (5-factor score of 0)
Consider – 

disease-modifying antirheumatic drug (DMARD)

Additional treatment recommended for SOME patients in selected patient group

The French Vasculitis Group have previously recommended that patients with a 5-factor score of 0 can be treated with corticosteroids alone, adding cyclophosphamide as second-line therapy only if there is persistent disease or relapse despite use of corticosteroids. However, this is associated with a 12% mortality.[68] A further study by the same group showed that 80% of patients with a 5-factor score of 0 achieved remission with corticosteroids alone, but remission was only sustained in 40%.[69] In patients who did not achieve remission or relapsed on corticosteroids alone, azathioprine or pulsed intravenous cyclophosphamide was used to induce remission successfully.[69]

However, a subsequent study by this group in 2017 showed no additional benefit, in terms of rate of remission or relapse, following the addition of azathioprine to treatment with prednisolone.[70]

If remission is not achieved with intravenous cyclophosphamide in 3 to 6 months, consider switching to oral cyclophosphamide until remission is achieved.

The British Society for Rheumatology guidelines on the management of ANCA-positive vasculitis recommends the use of methotrexate with corticosteroids to induce disease remission in disease with a good prognosis. Although there is no specific evidence for this regimen in PAN, the trial data in ANCA-positive vasculitis can be extrapolated to include PAN, and methotrexate is commonly used in practice.[59]

Primary options

cyclophosphamide: 15 mg/kg intravenously once every 2 weeks for 3 doses, then once every 3 weeks until remission, maximum 1200 mg/dose; or 2 mg/kg/day orally

OR

methotrexate: 7.5 to 15 mg orally once weekly on the same day each week initially, increase by 2.5 mg/week increments every 2-4 weeks according to response, maximum 25 mg/week

HBV-related PAN

1st line – oral prednisolone ± intravenous methylprednisolone

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ACUTE
|
HBV-related PAN
1st line – 

oral prednisolone ± intravenous methylprednisolone

Oral corticosteroids are given for 2 weeks, with the dose tapering during the second week, reaching 0 by the end of week 2.

In severely ill patients, intravenous methylprednisolone can be added for the first 1 to 3 days.

Primary options

prednisolone: 1 mg/kg/day orally for 7 days, then taper and withdraw by 14 days

OR

prednisolone: 1 mg/kg/day orally for 7 days, then taper and withdraw by 14 days

and

methylprednisolone: 15 mg/kg/day intravenously for 1-3 days

Plus – plasma exchange + lamivudine

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ACUTE
|
HBV-related PAN
Plus – 

plasma exchange + lamivudine

Treatment recommended for ALL patients in selected patient group

Plasma exchange and lamivudine are started immediately after the 2-week corticosteroid course.

Three plasma exchange sessions per week are given for 3 weeks, then 2 sessions per week for 2 weeks, then one session per week until there is seroconversion from HBeAg to HBeAb or the patient is clinically recovered and has been stable for 2 to 3 months. In each plasma exchange session, 60 mL of plasma/kg is replaced with 4% albumin.

Lamivudine is started with plasma exchange and continued for 6 months or until seroconversion to HBsAb. On days when a plasma exchange is performed, lamivudine should be taken after the session to avoid removal of the drug.

Care of patients with HBV-related PAN should always involve close consultation with a hepatologist, as there have been cases of fulminant hepatitis developing during acute treatment.[20]

Primary options

lamivudine: 100 mg orally once daily

ONGOING

relapse of disease

1st line – oral prednisolone: increased dose

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ONGOING
|
relapse of disease
1st line – 

oral prednisolone: increased dose

Patients who have a relapse on standard therapy should have their oral corticosteroid dose increased.

Primary options

prednisolone: 30 mg orally once daily, then taper gradually

Consider – disease-modifying antirheumatic drug (DMARD)

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ONGOING
|
relapse of disease
Consider – 

disease-modifying antirheumatic drug (DMARD)

Additional treatment recommended for SOME patients in selected patient group

In patients who have a major relapse (defined as being life- or organ-threatening disease), cyclophosphamide should be started or re-started, initially intravenously and then changing to oral therapy.

Primary options

cyclophosphamide: 15 mg/kg intravenously once every 2 weeks for 3 doses, then once every 3 weeks for 3-6 doses, maximum 1200 mg/dose, followed by 2 mg/kg/day orally, maximum 200 mg/day, to give a total of 3-6 months of treatment

Consider – intravenous methylprednisolone

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ONGOING
|
relapse of disease
Consider – 

intravenous methylprednisolone

Additional treatment recommended for SOME patients in selected patient group

Pulsed intravenous methylprednisolone can be given before each cyclophosphamide infusion, which may allow a faster tapering of oral corticosteroids.

Primary options

methylprednisolone: 10 mg/kg intravenously before cyclophosphamide infusions, maximum 1000 mg/dose

Plus – HBV serology + alternative antiviral therapy

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ONGOING
|
relapse of disease
|
HBV-related PAN
Plus – 

HBV serology + alternative antiviral therapy

Treatment recommended for ALL patients in selected patient group

HBV status should be checked initially on relapse and, if positive, needs to be eradicated before treatment for relapse of PAN.

The treating physician should liaise with his or her local hepatologists for advice about alternative antiviral therapy to treat HBV, rather than simply repeat the course of lamivudine.

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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