The application of methotrexate, rheumatoid arthritis patients have to know the precautions!

*For medical professionals only.
A brief introduction to methotrexate - the cornerstone of rheumatoid arthritis treatment
.

Methotrexate (MTX) is a classic drug in the treatment of rheumatic diseases.
This drug, which has benefited rheumatoid arthritis (RA) patients since 1951, still firmly occupies the first place in the RA guidelines of various countries.
take the top spot
.

However, the results of the China Rheumatoid Arthritis Direct Reporting Project (CREDIT) launched by the National Rheumatology Data Center (CRDC) show that the utilization rate of MTX in RA patients in China is only 55.
9%.
Or equipped with specialist doctors, the treatment concept is more standardized and in line with the diagnosis and treatment guidelines.
If it is expanded to the grassroots level, I am afraid this number will be greatly reduced
.

I can still often hear such words in my daily work: "How can RA take this drug? This is a chemotherapy drug
.

" "This drug is too toxic to the liver.
If RA is not cured, it will eat people bad.
" The worry is that these words come not just from patients, but from many doctors
.

From this point of view, it is still very necessary to specify the usage of MTX in detail
.

01 When to use MTX? The recommendations of the "2018 Chinese Guidelines for the Diagnosis and Treatment of Rheumatoid Arthritis" clearly point out that, once RA patients are diagnosed, they should start treatment with traditional synthetic disease-modifying antirheumatic drugs (csDMARDs) as soon as possible
.

Methotrexate monotherapy is recommended as the first choice (1A)
.

This is consistent with the RA guidelines of the European League Against Rheumatism (EULAR), the American College of Rheumatology (ACR) and the Asia Pacific League of Rheumatology (APLAR).

.

For the treatment of early undifferentiated arthritis, MTX was also recommended as the first-choice treatment in the EULAR recommendation in 2016, for early arthritis that persists and cannot be relieved or that there is sufficient evidence to indicate that it may develop in the direction of RA
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All in all, for patients with a clear diagnosis and no contraindications, the sooner MTX is used, the better! 02What should I pay attention to before using MTX? A summary of multiple randomized controlled studies found that contraindications for MTX use include severe kidney disease, liver disease, leukopenia <3.
0×109/L, thrombocytopenia <100×109/L, age greater than 70 years, malignant tumor, pregnancy or contraception Deficiency, history of alcohol/drug abuse, acute or chronic infection and lung disease
.

Therefore, before using MTX, it is recommended to evaluate relevant risk factors, improve blood routine, liver and kidney function, chest X-ray (within 1 year before the drug), viral hepatitis screening, pregnancy test, etc.
, and it is necessary to ask whether the patient has a history of alcohol/drug abuse , to judge the patient's comprehension ability and compliance, etc.
For patients with the above medical history, insufficient comprehension ability, and poor compliance, the medication should be adjusted as appropriate according to the condition
.

In addition, folic acid tablets should be taken orally in combination with MTX
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It is recommended to supplement folic acid 5mg per week during MTX treatment to reduce gastrointestinal adverse reactions
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03How about the dosage of MTX? Foreign guidelines recommend that the initial oral dose of MTX is usually 10-15mg/week, and if the patient's clinical response is good and can tolerate, it can be increased by 5mg every 2-4 weeks until 20-30mg/week
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Studies based on the Chinese population have shown that low-dose methotrexate (≤10 mg/week) has better safety and long-term tolerance
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If the dose is within 5-10mg/week, one-time administration is recommended.
If the dose is exceeded, it can be considered to be administered in two doses 6-12 hours apart
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04 The onset time and course of treatment of MTX "Kelly's Rheumatology" pointed out that regular use of MTX for 6 months can achieve the maximum effect, and it can be predicted whether it is effective or not at 3 months
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In national guidelines, it is also recommended to use MTX for at least 3 months before considering combination and replacement of other drugs
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However, in our country, most of the RA patients who are ineffective using MTX will stop taking the drug in the initial period of more than 1 month, which makes the efficacy of MTX not exerted and falls short
.

In addition, given that RA cannot be cured, MTX can be used for a long time on the basis of stable disease control and drug safety.
At present, there is insufficient evidence to show that MTX increases the risk of infection, lymphoma and malignancy
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05What is the effect of using MTX? A number of foreign studies believe that according to the dose of 20-25mg/week, about 50% of RA patients have good curative effect, and about 30% of patients can achieve a low disease activity state
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For Chinese patients, the regular dose of 10-15mg/week can achieve the purpose of effectively controlling RA
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Meta-analysis also showed that MTX has shown good effects in alleviating arthritis symptoms, reducing disability rate and delaying imaging structural damage
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06What are the indicators that need to be regularly evaluated when using MTX? When starting to use MTX or increasing the dose, it is recommended to check blood routine, liver and kidney function every month, and the monitoring time can be gradually extended (once in 1-3 months) after the drug dose and various indicators of the patient are stabilized
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Can 07MTX be used in combination with other DMARDs? MTX monotherapy is generally recommended initially for RA treatment
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However, for patients who do not meet the treatment target, it is recommended to combine one or two traditional synthetic DMARDs for treatment; or choose one traditional synthetic DMARDs combined with one biological agent or one targeted synthetic DMARDs for treatment
.

Reference: [1].
Jin S , Li M , Fang Y , et al.
Chinese Registry of rheumatoid arthritis (CREDIT): II.
?prevalence and risk factors of major comorbidities in Chinese patients with rheumatoid arthritis[J].
Arthritis Research & Therapy, 2017, 19(1):251.
[2].
Rheumatology Branch of Chinese Medical Association.
2018 Guidelines for Diagnosis and Treatment of Rheumatoid Arthritis in China [J].
Chinese Journal of Internal Medicine, 2018, 57(4):242[3 ].
Visser K.
Multinational evidence-based recommendations for the use of methotrexate in rheumatic disorders with a focus on rheumatoid arthritis : integrating systematic literature research and expert opinion of a broad international panel of rheumatologists in the 3E initiative[J].
Annals of the Rheumatic Diseases, 2009, 68(7):1086-1093.