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    Home > Active Ingredient News > Immunology News > How to properly use hormones for ANCA-associated vasculitis? Clinically essential

    How to properly use hormones for ANCA-associated vasculitis? Clinically essential

    • Last Update: 2023-01-07
    • Source: Internet
    • Author: User
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    ANCA-associated vasculitis (AAV) is a rare group of primary systemic necrotising small vessel vasculitiitis including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA).

    Among them, GPA and MPA account for about 80%-90%
    of all AAVs.
    Clinically appropriate treatment plans should be formulated according to the severity of AAV, patient age, weight, comorbidities, and prognosis1
    .
    Glucocorticoids (hereinafter referred to as hormones) are indispensable drugs in the treatment of AAV and play an important role
    in inducing remission and maintaining remission.
    This article will explain in detail the dosing and dosing
    of hormone therapy with AAV in conjunction with existing guidelines.


    1.
    Which AAV patients need hormone therapy?


    According to the 2022 new version of the EULAR guidelines2, patients with active GPA and MPA need to use hormone-induced remission, combined with rituximab, cyclophosphamide, or methotrexate
    .
    It is recommended to start with an oral hormone dose of 50 to 75 mg/day (prednisone, for example, adjusted for weight) and taper gradually to 5 mg/day
    over 4 to 5 months.
    Recommendation 3 of the 2021 ACR/VF guideline is to use intravenous pulse hormonal therapy or high-dose oral hormones, or oral methotrexate/rituximab, to induce remission in patients with active-severity EGPA; Remission induction of active, non-severe EGPA is treated with a combination of mepolimab/methotrexate/azathioprine/mycophenolate/rituximab, and some patients may consider steroids
    alone.


    Hormonal intravenous pulse: intravenous injection of methylprednisolone 500-1000mg/d (adults) or 30mg/kg/d (children's maximum 1000mg/d or equivalent dose, 3~5d
    .

    High-dose horticosteroid oral: prednisone 1 mg/kg/day (up to 80 mg/day for adults) or 1-2 mg/kg/day (up to 60 mg/day for children) or equivalent
    .


    In addition to patients with confirmed AAV, hormone therapy may be started in the absence of a clear diagnosis but high clinical suspicion (i.
    e.
    , while waiting for biopsy) to avoid diagnostic delay and subsequent worsening prognosis1
    .


    Second, how to reduce the amount of hormones?


    Reducing hormone-related adverse effects is an important consideration
    in the management of AAV.
    The 2021 ACR/VF guidelines also recommend hormonal tapering regimens rather than standard hormonal dose regimens for inducing remission3
    .
    The standard dose regimen of hormones refers to the initial dose (body weight< 50kg, 50mg/day; Weight 50~75kg, 60mg/d; body weight>75kg, 75mg/d); From week 3 to week 6, the dose is reduced by 10 mg every 2 weeks; The dose is reduced by 2.
    5-5 mg every 2-4 weeks starting at week 7 until it is reduced to 5 mg/day
    at week 23.
    The hormonal tapering regimen was used significantly less than the standard regimen, with the initial dose being the same as the standard regimen, with a dose reduction of approximately 50% at week 2; From weeks 3 to 6, the dose is reduced by 5 mg every 2 weeks; The dose is reduced by 1-2.
    5 mg every 2 weeks starting at week 7 until it is reduced to 5 mg/day at week 15; The cumulative 6-month dose of hormonal medication is less than 60%
    of the standard dosage regimen.


    In addition, faster hormonal tapering should be considered in patients with uncontrolled diabetes, obesity, severe osteoporosis, and prior hormone-related depression, anxiety, or psychiatric illness5
    .


    Are low-dose hormones equally effective?


    Whether the effective effect can be exerted while reducing the amount of hormones is a matter of clinical concern
    .
    Several RCTs have aimed to demonstrate that low-dose corticosteroids are comparable to high-dose regimens while reducing adverse effects1
    .
    The PEEXIVAS trial has shown that a faster hormonal tapering regimen (i.
    e.
    , to 20 mg/day [prednisone] within 7 weeks of initiation of therapy and 5 mg/day within 19 weeks) is as effective as the standard dose in patients with severe AAV who initially received methylprednisolone venous pulse therapy, and is safer with a lower
    risk of serious infection within 1 year.


    The LoVAS study included patients with new-onset non-severe AAV to assess the clinical prognosis
    of remission rate, remission time, recurrence rate, and adverse events of two remission-inducing regimens: rituximab combined with low-dose (0.
    5 mg/kg/day) or high-dose hormone (1 mg/kg/day).
    Results showed that 0.
    5 mg/kg/day hormone was sufficient to induce remission and reduce the incidence of
    gammaglobulinemia.
    These findings may drive "low-hormone therapy" for AAV, i.
    e.
    , reducing hormone dose and duration, thereby reducing cumulative dose
    .


    Hormones have a wide range of anti-inflammatory effects in AAV treatment, and many guidelines such as EULAR, ACR/VF clearly recommend hormone therapy for AAV
    .
    In the course of administration, low-dose hormones effectively induce remission while reducing the risk of adverse effects and appear to be a better treatment option, a view
    supported by several RCT studies.
    In short, with the accumulation of clinical research results, the treatment drugs and treatment plans of AAV are constantly being optimized, and it is expected that the disease management will be more perfect and patients will benefit
    to a greater extent in the future.


    References:

    1.
    Chevet B, Cornec D, Casal Moura M, Gall EC, Fervenza FC, Warrington KJ, Specks U, Berti A.
    Diagnosing and treating ANCA-associated vasculitis: an updated review for clinical practice.
    Rheumatology (Oxford).
    2022 Oct 31:keac623.
    doi: 10.
    1093/rheumatology/keac623.
    Epub ahead of print.
    PMID: 36315063.

    2.
    Bernhard Hellmich.
    EULAR2022 Virtual Congress.
    oral presentationat 1nd Jun.

    3.
    Yu Xiaoyong.
    2021 American College of Rheumatology/Vasculitis Foundation guidelines for the treatment of antineutrophil cytoplasmic antibody-associated vasculitis[J].
    Shaanxi Medical Journal,2022,51(3):259-269,307.
    DOI:10.
    3969/j.
    issn.
    1000-7377.
    2022.
    03.
    001.

    4.
    Zeng L, Walsh M, Guyatt GH, et al.
    Plasma exchange and glucocorticoid dosing for patients with ANCA-associated vasculitis: a clinical practice guideline[J].
    BMJ.
    2022 Feb 25; 376:e064597.
    doi: 10.
    1136/bmj-2021-064597.

    5.
    Patel NJ, Stone JH.
    Expert Perspective: Management of ANCA-AssociatedVasculitis[J].
    Arthritis Rheumatol.
    2022 Mar 14.
    doi: 10.
    1002/art.
    42114.
    Epub ahead of print.

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