Can gout patients take the medicine twice a month, can the uric acid be lowered?

*It is only for medical professionals to read for reference.
It is so difficult for gout patients! Hyperuricemia (HUA) refers to the fasting blood uric acid level of men> 420 μmol/L and women> 360 μmol/L on different days under a normal purine diet
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Gout is caused by the formation and deposition of sodium urate crystals in the joints due to blood uric acid exceeding its saturation in the blood or tissue fluid, which induces local inflammation and tissue destruction.
It belongs to the category of metabolic rheumatism, including diabetes, metabolic syndrome, The independent risk factors for dyslipidemia, chronic kidney disease (CKD) and stroke, etc.
, can be divided into 4 stages according to the course of the disease, namely, asymptomatic hyperuricemia, acute gouty arthritis, and gouty arthritis Intermittent episodes, chronic gouty arthritis
.

Refractory gout (RCG) refers to the occurrence of chronic multiple and destructive arthritis after repeated attacks of acute gouty arthritis for several years, accompanied by the formation of tophi and/or uric acid kidney stones.
It is difficult for conventional doses of uric acid-lowering drugs to treat Gout with blood uric acid up to standard often manifests as continuous joint swelling, pain, multiple tophi and joint destruction, and poor quality of life
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RCG has at least one of the following three items, namely, single or combined use of conventional uric acid lowering drugs in sufficient quantity and full course of treatment, but blood uric acid is still ≥360μmol/L; receiving standardized treatment, gout still attacks ≥2 times/year; present Multiple and/or progressive tophi
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The "Chinese Guidelines for the Diagnosis and Treatment of Hyperuricemia and Gout (2019)" also pointed out: In recent years, a number of RCG clinical studies have defined baseline blood uric acid ≥480 μmol/L and the presence of at least one of the following clinical features as refractory gout, namely In the past 18 months, there have been more than 3 attacks of gout; at least 1 tophi; persistent joint pain or imaging showing gout-related joint damage; allopurinol is contraindicated, or blood uric acid when the maximum dose is used for more than 3 months Those who still do not meet the standard
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The treatment principle of RCG is mainly to reduce blood uric acid level and improve clinical symptoms
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New uric acid-lowering drugs can be used in the treatment of RCG to lower blood uric acid levels; biological agents can be used in the acute stage of RCG and can quickly control symptoms
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1 New-type uric acid lowering drugs such as polyethylene glycol recombinant uricase preparation Pegloticase, recombinant Aspergillus flavus urate oxidase Rasburicase
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①Pegloticase Pegloticase (polyethylene glycol recombinant uricase preparation) is a biological preparation formed by the covalent combination of uricase and monomethoxypolyethylene glycol, which can quickly and powerfully reduce blood uric acid and reduce the deposition of urate crystals.
Most RCGs have good curative effects and can be used for patients with refractory gout, or disabled gout patients whose traditional uric acid-lowering drugs are ineffective
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It is recommended that Pegloticase 8mg, administered once every two weeks, has the best effect and has the least adverse effects
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The pharmacokinetics of Pegloticase is not affected by age, sex, weight and creatinine clearance
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Compared with Rasburicase, it has a longer half-life and higher bioavailability, but long-term use may produce high-titer Pegloticase antibodies, resulting in poor therapeutic effects
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Studies have shown that Pegloticase has no significant effect on the eGFR of patients with chronic renal insufficiency, and the response to Pegloticase treatment has nothing to do with its CKD stage
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Intravenous infusion of Pegloticase has a high-efficiency and long-lasting effect of lowering uric acid, and has a faster dissolution effect
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It may play a bridging role in the treatment of RCG.
First, Pegloticase is used to quickly clear uric acid, and then conventional uric acid-lowering drugs are used after the tophi is dissolved
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According to the "Research Progress of Biological Agents in the Treatment of Refractory Gout" (2020), the use of Pegloticase can easily induce acute attacks of gout and infusion-related reactions (IRs), and may worsen existing cardiovascular diseases.
It is recommended to give small doses before use.
Dose of colchicine or non-steroidal anti-inflammatory drugs (NSAIDs) to prevent gout attacks, use antihistamines and glucocorticoids to prevent IRs when necessary
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Note: Adverse reactions include nausea, vomiting, blushing, headache, musculoskeletal pain, erythema, blood pressure changes, dyspnea, urticaria, allergic reactions and infusion reactions, etc.
, which mostly occur in people with high anti-Pegloticase antibody titer.
Medication is recommended Antihistamines and glucocorticoids were given before prevention to reduce the occurrence of adverse reactions
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Other serious cardiovascular events, such as gout
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Avoid use in people with glucose-6-phosphatase (G-6-PD) deficiency to prevent increased risk of hemolysis and methemoglobinemia
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People with cardiovascular disease should avoid using Pegloticase to prevent heart failure from aggravating
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②Rasburicase Rasburicase is a recombinant Aspergillus flavus urate oxidase, approved by the U.
S.
Food and Drug Administration (FDA) in 2010 for the treatment of RCG or gout intolerant to conventional treatment, and for the prevention and treatment of hematological malignancies Acute HUA is especially suitable for HUA caused by radiotherapy and chemotherapy
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Recommended /d 0.
2mg/kg administration
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Compared with the traditional drug allopurinol, Rasburicase has a faster onset of action, which can reduce uric acid that has been deposited while reducing uric acid
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It is mainly degraded by hydrolyzed peptides, renal excretion is the second way, and the pharmacokinetics has nothing to do with the degree of renal damage, so it has a better effect on gout patients with renal insufficiency
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Note: It can induce antibody production and decrease the efficacy
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Rasburicase has strong antigenicity and is prone to allergies after long-term use
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Because the effect of lowering uric acid is rapid, and a sharp drop in uric acid level can induce acute attacks, those who are sensitive to fluctuations in serum uric acid level should be used with caution
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Those with G-6-PD deficiencies are forbidden
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Avoid the combination of Rasburicase and allopurinol during use, because the latter inhibits xanthine oxidase and will reduce the efficacy of Rasburicase
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2 Biological preparations Acute gouty arthritis usually occurs in a single joint of the lower limbs.
It has a rapid onset, severe disease, and rapid change.
It can develop to a peak within 6 hours.
The joints and surrounding soft tissues have obvious redness, swelling, heat and pain, and the pain is severe
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When large joints are involved, there may be joint exudate, and may be accompanied by systemic symptoms such as headache, fever, and increased white blood cell count
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Possible predisposing factors include local joint damage (such as trauma), cold, moisture, tight shoes, excessive walking, eating, drinking, surgery, dehydration, fatigue, drugs, and infections
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Interleukin-1 (IL-1) antagonists, tumor necrosis factor alpha (TNF-α) inhibitors, and IL-6 inhibitors can be used for the treatment of acute attacks of gout
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According to the "Chinese Guidelines for the Diagnosis and Treatment of Hyperuricemia and Gout (2019)" (2020), patients with recurrent pain and refractory gout that cannot be controlled by conventional drugs may consider using IL-1 or TNF-α inhibitors
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①IL-1 antagonist IL-1β is the initiating factor of the inflammatory response caused by the deposition of pathogenic crystals, and IL-1 is one of the most powerful inflammatory mediators in the body
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According to the "Guidelines for the Diagnosis and Treatment of Hyperuricemia and Gout in China (2019)" (2020), IL-1 antagonists of new gout anti-inflammatory and analgesic drugs can be used for the treatment and prevention of gout, such as anakinra and kanadan Anti-Linazep
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Anakinra is a recombinant human IL-1 receptor antagonist.
The American College of Rheumatology (ACR) recommended Anakinra for the treatment of severe acute gouty arthritis in 2011
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It does not affect kidney function and has a short half-life
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Studies have shown that Anakinra can effectively alleviate the inflammatory response in the acute stage of gout.
It has a good effect on the three crystal arthritis (CRIA) of gout, pseudogout and hydroxyapatite deposition disease.
It is combined with colchicine Alkali is more effective in the treatment of refractory CRIA
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It is not recommended to use it in combination with other biological agents because it will cause serious adverse events including an increased incidence of serious infections
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Kanazumab is an anti-IL-1β monoclonal antibody with a longer half-life than anakinra.
ACR recommended Kanazumab for the treatment of severe acute gouty arthritis in 2012.
Kanazumab was used in the treatment of severe acute gouty arthritis in 2013.
Anti-Gout is approved by the European Medicines Agency (EMA) for the treatment of acute attacks of gout that are intolerant or contraindicated with conventional anti-inflammatory and analgesic drugs
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Studies have shown that Kanazumab can reduce the risk of acute gout attacks
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Linazep is a bispecific human IgG1Fc antibody that can bind to IL-1β and block its biological activity.
It can effectively prevent the acute attack of gout, especially the acute attack of gout in the early stage of lowering uric acid
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According to the "Guidelines for the Diagnosis and Treatment of Hyperuricemia and Gout in China (2019)" (2020), although Linazep is effective in preventing gout, it has not yet been recommended by international authorities
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② Studies of TNF-α inhibitors show that TNF-α is a key factor causing rheumatoid arthritis (RA) synovial inflammation
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TNF-α inhibitors such as etanercept and infliximab have been reported in the literature for the treatment of gout, but further research is still needed
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Studies have shown that etanercept can relieve joint swelling and improve uric acid levels
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Case reports infliximab can improve joint inflammation and reduce inflammation indicators
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③IL-6 inhibitors such as tocilizumab
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Tocilizumab is a humanized anti-IL-6 receptor IgG1 subtype antibody, which can prevent the transmission of IL-6 signals and inhibit the chain reaction of inflammation
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There are reports of tocilizumab treatment of chronic gouty arthritis with fever
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④Other Abatacept is a soluble fusion protein consisting of cytotoxic T cell associated protein (CTLA)-4 and the Fc segment of IgG1
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Studies have reported that Abatacept can reduce the frequency of gout attacks
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Adverse reactions include headache and nausea, which may increase the incidence of infection and tumors
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Note: Adverse reactions of biological agents are injection site reactions or infusion reactions, which increase the risk of tuberculosis infection, hepatitis virus activation and tumors.
Others include heart failure and skin reactions
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TNF-α inhibitors occasionally have drug-induced lupus-like syndromes and demyelinating diseases
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The application progress of biologics in the treatment of gout[J].
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Chinese Journal of Frontiers in Medicine ,2013,5(3):49-50 Source of this article: Rheumatology Channel of the Medical Circle Author of this article: Gao Lili Review of this article: Deputy Chief Physician Chen Xinpeng Editor: Cassette Copyright Statement