Prof. Leng Xiaomei: If the "anchoring drugs" for RA treatment does not work, what traditional synthetic drugs are available?

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。
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。
“MTX，DNA、[6]
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Professor Leng Xiaomei pointed out that from the perspective of efficacy, due to the complexity of RA disease, the therapeutic effect of a single drug is relatively limited.
According to the survey, 72% of patients did not reach the therapeutic target after receiving MTX monotherapy (DAS28- at week 24).
ESR≤3.
2)[7]
.

From the point of view of safety, since MTX has an important influence on cell metabolism, its side effects are relatively obvious
.

The main adverse reactions of MTX include gastrointestinal reactions and damage to liver and kidney functions, which are intolerable for some patients, and thus cannot receive full-dose and full-course treatment.
During the use of MTX, it is necessary to Closely monitor the occurrence of adverse reactions [6]
.

 "In the clinic, the phenomenon of reducing the dose of MTX or even stopping the drug due to side effects has occurred from time to time.
How to meet the treatment needs of these patients is a very real problem before us
.

" Professor Leng Xiaomei said that at present, MTX in RA patients in China The utilization rate of the system is only 55.
9%[8], which is far lower than the average level of other countries (83%)[9]
.

In order to better meet the needs of clinical medication, starting from the disease mechanism, exploring more treatment options to expand treatment options is an important research direction in current RA clinical research
.

 Don't just catch a "sheep" for wool, is there any other suitable substitute? What happens when MTX, the first-line drug for RA treatment, doesn't work or doesn't work? Don't just catch a "sheep"! At present, the relevant guidelines for the treatment and management of RA in various countries in the world suggest that if patients have contraindications to the use of MTX, or the efficacy is not satisfactory, other commonly used csDMARDs can be used for treatment [3-4]
.

"DMARDs can be divided into three main categories: csDMARDs, biologics (bDMARDs), and targeted synthetic DMARDs (tsDMARDs)
.

"Professor Leng Xiaomei introduced, "In addition to MTX, csDMARDs also include leflunomide (LEF), sulfasalazine (SASP), hydroxychloroquine (HCQ), islamod (IGU) and so on
.

"When MTX is not effective or patients can't tolerate it, we can switch patients to other csDMARDs, or use a combination therapy regimen -- combined with other csDMARDs or bDMARDs/tsDMARDs
.
"
"Professor Leng Xiaomei pointed out that based on the fact that csDMARDs are still the basis of the current RA treatment, it is very necessary to explore new, effective, tolerable and affordable oral csDMARDs to help the majority of patients achieve their treatment goals
.

 Category 1.
1 independently developed by China The new drug IGU is a new type of csDMARD with multiple targets and multiple mechanisms, which can inhibit the classical immune pathway and exert anti-inflammatory and bone metabolism effects
.

Professor Leng Xiaomei pointed out that in Japan and China, IGU has been widely used as a new type of csDMARD.
For the treatment of RA, the efficacy and safety have been proved by many clinical studies and clinical practice[10-18]
.

 How to maximize the benefits of single drug or combination therapy? Combination therapy is currently the treatment option for moderate to severe RA.
The purpose is to combine drugs with different mechanisms of action to prevent abnormal immune responses and immune damage in different links, and play an additive or synergistic role in curative effects.
19 The pathogenesis of RA is very complex, and various immune cells and
cytokines
Participate in it, therefore, the combined drug may play the role of "1+1>2"
.

Professor Leng Xiaomei said that the combined treatment of IGU and MTX is not only more effective than MTX monotherapy [20-21], but also compared with other When compared with the combination of csDMARDs + MTX, the overall efficacy is comparable, and the safety is better (Table 1) [14]
.

Table 1: Relevant studies of MTX combined with IGU therapy [14, 20-21] "For patients with RA with less severe disease, we can choose monotherapy
.

" Previous clinical studies have shown that IGU monotherapy is not inferior to the efficacy of RA In other csDMARDs (such as MTX, SASP), and well tolerated (Table 2) [22-23]
.

Therefore, as a new type of small molecule DMARDs, whether it is a single drug or a combination therapy, IGU has good efficacy and safety in the treatment of RA
.

Table 2: Studies related to IGU monotherapy[22-23] At present, there are many international guidelines or consensuses on the diagnosis and treatment of RA
.

IGU has accumulated a wealth of evidence-based medical evidence, so we have also seen IGU in some of the guideline recommendations
.

"The R&D and application of IGU is mainly concentrated in China and Japan, and it has been approved for marketing in these two countries
.

" Professor Leng Xiaomei pointed out, "The guidelines issued by the Asia-Pacific Association of Rheumatology Associations (APLAR) in 2015 and 2018 recommended that It is pointed out that RA patients who are intolerant to MTX can receive other csDMARDs as first-line treatment, such as LEF, SASP and HCQ.
In some Asia-Pacific countries, new drugs such as IGU may also be considered as options [4-5]; The Guidelines for the Diagnosis and Treatment of Rheumatoid Arthritis [3] and the newly released Guidelines for the Diagnosis and Treatment of Rheumatoid Arthritis in 2022 [24] also cited relevant research reports on IGU, and IGU was included in the commonly used csDMARDs
.

Data are limited, and IGU is rarely mentioned in RA guidelines or consensus in these countries
.

 When talking about the application of IGU in real clinical practice, Professor Leng Xiaomei said that since its launch in 2011, we have accumulated a lot of experience in using IGU in clinical practice
.

"In the clinical treatment of RA, we are more accustomed to choosing the combination therapy
.

The efficacy and safety of IGU in the combination therapy are relatively guaranteed, and it can be used as one of the combination therapy options
.

" Professor Leng Xiaomei said, "about For the adjustment of drug types and doses during treatment, we tend to 'de-escalate'—that is, after the combination therapy stabilizes, gradually reduce the types and/or doses of drugs, and try to maintain the least types and doses of drugs.
Disease remission
.

” Finally, Professor Leng Xiaomei said that from the current clinical evidence, IGU has good efficacy and safety in the treatment of RA, and can be used as a potential alternative to MTX for MTX intolerance or response Poor RA patients can also be treated with other DMARDs to achieve higher treatment goals
.

"I believe that with the accumulation of time in the future, there will be more large-scale and high-quality clinical studies to further confirm its efficacy and long-term safety
.

" Conclusion With the increasing abundance of RA treatment drugs, there are more clinical treatments of selectivity
.

Although MTX is the anchor drug in the treatment of RA, when a patient has a contraindication or insufficient response to MTX, combination therapy or switching therapy should be considered
.

IGU is a new type of DMARD, which has both efficacy and safety in the treatment of RA.
It can be used alone or in combination, which can further meet the clinical treatment needs of RA patients
.

Expert Profile Prof.
Leng Xiaomei Chief Physician, Professor and Doctoral Supervisor of the Rheumatology and Immunology Department of Peking Union Medical College Hospital Deputy Secretary-General of the Chinese Rheumatology and Immunology Medical Association Deputy Head of the Osteoporosis Group of the Rheumatology Branch of the Chinese Medical Doctor Association Cross-Strait Medical and Health Exchange Deputy head of the psoriatic arthritis group of the Rheumatology and Immunity Branch of the Society, an expert in food and drug inspection from the State Food and Drug Administration, presided over and participated in a number of topics such as SLE, RA, SpA References: [1] Fraenkel L, Bathon JM, England BR, et al.
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