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    Home > Active Ingredient News > Immunology News > NEJM sub-issue: Allopurinol VS Febuxostat, who is better?

    NEJM sub-issue: Allopurinol VS Febuxostat, who is better?

    • Last Update: 2022-04-30
    • Source: Internet
    • Author: User
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    *For reference only for medical professionals, they are all first-line drugs.
    Is there really a difference? On February 3, 2022, a sub-journal of the New England Journal of Medicine (NEJM Evidence-Based) officially published a comparative study on the efficacy of allopurinol and febuxostat in the treatment of gout.
    Whether there is a difference between the safety, uric acid-lowering efficacy and control of gout flares of febuxostat in the treatment of gout
    .

     "Medical Rheumatism and Immunity Channel" specially invited Professor Ling Guanghui from the Second Xiangya Hospital of Central South University to give a detailed interpretation to the readers
    .

     STUDY ABSTRACT Swipe up for background: The relative efficacy and safety of allopurinol and febuxostat in the treatment of hyperuricemia according to current guidelines is unknown
    .

    This double-blind noninferiority trial was designed to address this question
    .

    Methods: In this 72-week trial, participants with gout and hyperuricemia [at least 33% with stage 3 chronic kidney disease (CKD)] were randomly assigned to allopurinol or febuxostat In the treatment group, the dose was titrated to achieve the target serum urate level
    .

    The trial is divided into three phases: a treatment phase (weeks 0-24), a maintenance phase (weeks 25-48), and an observation phase (weeks 49-72)
    .

    The starting doses of allopurinol and febuxostat were 100 mg and 40 mg, respectively, and the maximum titrated doses were 800 mg and 120 mg, respectively
    .

    Anti-inflammatory prophylaxis was given in stages 1 and 2
    .

    The primary endpoint was the proportion of patients who experienced one or more gout flares during Phase 3, and secondary endpoints included efficacy in patients with CKD, proportion achieving target serum urate levels, and serious adverse events
    .

    Results: In this study of 940 participants, in Phase 3, 36.
    5% of allopurinol-treated participants experienced one or more episodes compared with 43.
    5% of non-buxostat-treated participants (noninferiority).
    P<0.
    001)
    .

    Overall, 80% of participants achieved target serum urate levels in Phase 2, and there were no differences in treatment outcomes or serious adverse events (including cardiovascular events) between the two groups
    .

    Conclusions: Allopurinol and febuxostat achieved serum urate targets in patients with gout; allopurinol was noninferior to febuxostat in attack control; also observed in participants with stage 3 CKD Similar results
    .

    To find out, why is febuxostat more widely used in clinical practice? QMedical community: At present, there are about 130 million hyperuricemia patients in my country, and the use of drugs is a hot topic.
    How about the clinical use of allopurinol and febuxostat, two uric acid-lowering drugs? Professor Ling Guanghui: With the development of China's economy, the incidence of hyperuricemia and gout patients has gradually increased.
    Allopurinol and febuxostat are common clinical drugs that inhibit uric acid synthesis.
    It is widely used in clinical practice.
    Relatively speaking, febuxostat is used more widely.
    The main reasons are as follows: Considering that allopurinol can cause fatal hypersensitivity reactions in yellow people, large-scale tertiary hospitals have There are certain restrictions on use
    .

    At present, multiple guidelines at home and abroad recommend that patients with gout of East Asian ethnicity should undergo HLA-B*5801 genetic testing before treatment with allopurinol
    .

    And most patients can only go to a third-party testing company for this test, which limits its use
    .

    Head-to-head high-quality research, once again for the clinical "building blocks" Q medical community: This study compared the safety and efficacy of allopurinol and febuxostat, could you please briefly introduce the background of the study and its uniqueness What? Professor Ling Guanghui: There is currently a lack of clinical data on the relative efficacy and safety of allopurinol and febuxostat, the two main oral uric acid-lowering drugs.
    The innovation of this study lies in the head-to-head comparison of these two drugs.
    high quality research
    .

     A total of 940 participants were included in the study, and one-third of the patients had stage 3 chronic CKD.
    All patients were randomly assigned to allopurinol or febuxostat treatment groups.
    The trial was divided into 3 phases: uric acid-lowering treatment phase (Weeks 0-24): During this period, allopurinol or febuxostat treatment groups were started at doses of 100 mg and 40 mg per day, respectively, until serum urate was below 360 μmol/L (if tophi was present, then less than 300 μmol/L) or the maximum dose has been reached (maximum titrated doses are 800 mg and 120 mg, respectively)
    .

    Maintenance phase (weeks 25 to 48): According to the guideline recommendations, in phases 1 and 2, all participants will need to receive prophylactic anti-inflammatory therapy with colchicine, NSAIDs, or glucocorticoids
    .

    Dose adjustment of allopurinol and febuxostat was allowed until week 33 to achieve serum urate targets
    .

    Observation period (weeks 49-72): No dose adjustment is allowed, and all prophylactic anti-inflammatory treatments are discontinued
    .

    But preventive treatment can be restarted at the onset of gout
    .

    The head-to-head study has a large sample size, strong data representation, and a trial period of up to 72 weeks
    .

     However, it also has certain limitations: Compared with the initial dose of 20-40 mg/d of febuxostat given in China, the 40 mg/d febuxostat in this study can lead to excessive uric acid lowering
    .

    In addition, the maximum dose of allopurinol in this study is 800mg, while China advocates that the maximum dose of allopurinol is less than 600mg, generally 500-600mg, and they are all for specific patients.
    For routine patients, about 300mg of allopurinol can achieve a good effect
    .

    The maximum dose of febuxostat in this study was 120 mg, and taking into account liver damage, more than 80 mg should be used with caution
    .

    Although there are certain limitations, in general, the data of this study are representative and of high quality, and have certain guiding significance for clinical practice
    .

     It is very important to use small doses to avoid adverse reactions.
    Q medical community: The study found that there was no significant difference in the incidence of serious adverse events caused by allopurinol and febuxostat.
    What do you think of this? Prof.
    Ling Guanghui: At present, domestic and foreign guidelines for gout patients emphasize uric acid-lowering treatment.
    In addition to allopurinol and febuxostat, Chinese guidelines also recommend benzbromarone as the first-line drug for uric acid-lowering therapy
    .

    As a clinician, it is most important to choose the appropriate drug according to the patient's characteristics, and to start with a small dose and gradually reach the target
    .

     Everyone is encouraged to perform HLA-B*5801 genetic testing before using allopurinol according to the requirements of the guidelines, but some primary hospitals lack other drugs, and only allopurinol can be selected, so it is recommended to start with a small dose (50~100 mg/d) ), monitor the blood uric acid level once every 4 weeks, and the patients who do not meet the standard can increase by 50-100 mg each time, and gradually increase to 300 mg/d, so that the incidence of adverse reactions will be relatively lower
    .

     Although febuxostat is warned by the FDA in a black box, as long as it is used at a low dose (20 mg/d) and gradually explores a maximum dose adapted to the patient, it is safe for the treatment of gout patients
    .

     Although the curative effect is the same, there are still differences in the use of drugs.
    Q: Research shows that allopurinol is not inferior to febuxostat in the treatment and control of gout patients.
    What guiding significance do you think this has for clinical practice in my country? Professor Ling Guanghui: The conclusion of this study once again emphasizes that both drugs are used as first-line treatment for lowering uric acid in clinical practice
    .

    Although allopurinol is a classic old drug, some patients in our country cannot tolerate it, and about 2% of the patients may have severe "allopurinol hypersensitivity syndrome" during the use of allopurinol, and some studies have reported its mortality rate Probably more than 20%, so unless genetic testing is done, it's not necessarily the most appropriate recommendation as the number one recommendation
    .

    Two other drugs, febuxostat and benzbromarone, are relatively more suitable for recommendation
    .

     It is worth noting that there are currently few first-line options for uric acid-lowering drugs, and there are only three drugs in total.
    A study in Japan found that single-drug treatment or a combination of two drugs in patients with refractory gout was not good for uric acid-lowering treatment, but combined with After allopurinol, the uric acid-lowering effect is enhanced.
    Therefore, as the main force of gout, allopurinol should be included in the treatment options despite its potential risks
    .

    Expert Profile Professor Ling Guanghui Deputy Director of Department of Rheumatism and Immunology, Second Xiangya Hospital of Central South University, Master Supervisor, Doctor of Medicine, Associate Professor Member of Rheumatology and Immunology Branch of Chinese Medical Doctor Association, Member of Academic Committee of Immunoadsorption of Chinese Medical Doctor Association Member of Chinese Medical Association Psychosomatic Medicine Branch Psychosomatic Rheumatism Collaboration Member of the study group, member of the Rheumatology Society of the China Association for the Promotion of International Exchanges in Health Care, member of the Osteoporosis Group of the China Association for the Promotion of International Exchange of Health Care Director, visiting scholar at UAB University School of Medicine References: [1] James R, O Dell, Mary T, et al.
    Comparative Effectiveness of Allopurinol and Febuxostat in Gout Management.
    NEJM Evidence, 2022; 1 (3) DOI: https: https://doi.
    org/10.
    1056/EVIDoa2100028
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