Lupus patients must pay attention to avoid these major medication "minefields"

*It is only for medical professionals to read for reference.
SLE is no longer an "immortal cancer"! Systemic lupus erythematosus (SLE) is a systemic autoimmune disease.
The main clinical features are multi-system and multi-organ involvement, repeated recurrence and remission, and the presence of a large number of autoantibodies in the body.
If not treated in time, it will cause affected organs.
Irreversible damage to the organ will eventually lead to the death of the patient.

The etiology of SLE is complex and is related to multiple factors such as heredity, sex hormones, and environment (such as viral and bacterial infections).

The prevalence of SLE in mainland China is about 30 to 70 per 100,000, and the male to female prevalence ratio is 1:10 to 12 [1].

So what are the precautions for patients with SLE? What are the common misunderstandings? The editor will come for you one by one.

1.
"Lupus can do everything!" SLE is a type of highly heterogeneous disease.
Each patient has a different performance.
The milder is just skin and joint lesions, and the severer has blood system damage, kidney, heart, lungs, etc.
Damage to important organs may even involve the central nervous system, resulting in neuropsychiatric lupus.

However, it is easy to be misled.
Although the most typical and well-known symptom of SLE is facial butterfly erythema, the first symptom is skeletal muscle pain (70%-80%)! Figure 1 Characteristics of SLE patients in China At present, the diagnosis of SLE is mainly based on the 2019 European Union Against Rheumatism/American College of Rheumatology (EULAR/ACR) SLE classification criteria.
Clinicians score the patient's condition, and the total score ≥10 can be classified.
For SLE.

For SLE patients who are newly diagnosed and followed up, it is recommended to select the SLE Disease Activity Index (SLEDAI-2000) scoring standard, and evaluate the disease activity in combination with the comprehensive judgment of the clinician.

The current consensus is that the disease should be controlled in the ideal state of clinical remission.
If clinical remission cannot be achieved, the disease activity should be controlled at the lowest possible disease activity level.

Among SLE patients with a course of ≤ 4 years, about 25% of patients can achieve clinical remission after treatment, and 45% of patients have organ damage.

Recurrence is a common clinical feature of SLE patients.
Studies have shown that the total risk of recurrence in SLE patients within 4 years is 60%.

2.
To bypass the misunderstanding and follow the guideline how to treat SLE medications? We have listed the common clinical misunderstandings in the treatment of SLE, and provided the current common drugs for SLE according to the "2020 China Systemic Lupus Erythematosus Guidelines" and the "2019 European Anti-Rheumatism Alliance Recommendations for the Treatment of Systemic Lupus Erythematosus Updates" The choice and usage.

▎Misunderstanding 1: Taboo doctors self-administer medication.
Many people believe that the treatment of SLE is nothing more than hormones, immunosuppressants, etc.
, and believe that everyone's treatment plans are similar, causing these patients to have symptoms such as muscle soreness for the first time or when SLE relapses Self medication.

Just like the cooking of senior chefs and novices in the kitchen, the same ingredients are used to make the taste but different.

The amount of condiment determines the final taste! The use of drugs is the same.
Although the types of drugs are similar, the dosage and usage of each person needs to be customized by the doctor.

According to the "Guidelines for Diagnosis and Treatment of Systemic Lupus Erythematosus in China 2020", the treatment principle of SLE is early and individualized treatment, which can delay disease progression to the greatest extent, reduce organ damage, and improve prognosis.

Individualized medication is essential for SLE.

▎Misunderstanding 2: Symptoms improve and stop the drug by itself.
Because SLE has the characteristics of alternating relapse and remission, some patients take medicine with symptoms, and the symptoms disappear and stop the drug.

This approach is very wrong.

Recurrence is a common clinical feature of SLE patients.
Studies have shown that the total risk of recurrence in SLE patients within 4 years is 60%, and the condition after recurrence may be aggravated and drug resistance enhanced.

In view of this, one of the long-term goals of SLE treatment is to reduce recurrence.
After disease remission or minimum disease activity is reached, treatment strategies usually need to be adjusted to prevent and reduce recurrence.

Hydroxychloroquine: On the premise of no contraindications, it is recommended that all patients use hydroxychloroquine as a basic treatment for a long time; for patients taking hydroxychloroquine, it is recommended that they undergo eye-related risk assessment: high-risk patients are recommended to have an eye examination once a year.
Low-risk patients are recommended to undergo eye examinations once a year from the 5th year of taking the drug.

Hormones: Hormone drugs are currently recognized as the fastest-acting drugs for controlling rheumatism.
They are the most commonly used SLE inducing remission treatment and are unanimously recommended by domestic and foreign guidelines to control SLE disease.

However, there are huge differences in understanding about hormone therapy in most patients.

▎Misunderstanding 3: Hormone understanding is two extremes.
On the one hand, the abuse of hormones persists.

Long-term high-dose use of hormones has many serious adverse effects.
SLE can only use the lowest dose of hormones to control the disease during the active period of the disease, and gradually reduce the dose to stop the drug after the disease is stable.

On the other hand, more and more people are "talking about hormone discoloration.
" It is undeniable that hormone drugs are currently recognized as the fastest-acting drugs to control rheumatism, and the use of hormones to treat rheumatism can often be effective.
To a good effect.

Hormones are the basic drugs for the treatment of SLE; individualized hormone treatment programs should be formulated according to the disease activity and the type and severity of the organs involved, and the lowest dose required to control the disease should be adopted.

For mildly active SLE patients, hormones are generally not needed, but when the efficacy of hydroxychloroquine or non-steroidal anti-inflammatory drugs is not good, low-dose hormones (≤10 mg/d prednisone or other equivalent doses) may be considered Hormone); For moderately active SLE patients, hormone [0.
5~1 mg (kg·d)] prednisone or other hormones in equivalent doses) combined with immunosuppressive agents can be used for treatment; for severely active SLE patients, Hormone [≥1 mg (kg·d) prednisone or other hormones in equivalent doses] combined with immunosuppressive agents can be used for treatment.
After the condition is stable, the hormone dosage should be adjusted appropriately.

Clinicians need to pay close attention to the disease activity of patients with SLE and adjust the hormone dosage according to the disease activity.
For patients with long-term stable disease, consider gradually reducing the dose after 2 or 6 weeks after the disease is stabilized to avoid recurrence of the disease and avoid sudden disease.
Severe cortical insufficiency occurred after stopping the drug.

The incidence of hormonal adverse reactions exceeds 30%.
Studies have shown that SLE patients receiving >7.
5 mg/d prednisone are more likely to develop hormone-related cardiovascular diseases (including myocardial infarction, heart failure and cerebrovascular disease), kidneys, musculoskeletal, etc.
Damage, and receiving ≤7.
5 mg/d prednisone treatment has nothing to do with cumulative damage in SLE patients.

▌Immunosuppressive agents: ▎Misunderstanding 4:Immunosuppressive agents have serious adverse reactions? The adverse reactions of different immunosuppressive agents are different, such as bone marrow transplantation, co-infection, gastrointestinal reactions, liver and kidney damage.
.
.
But due to the remarkable effect of immunosuppressants on treatment, we should not give up food due to choking.

Checking the liver and kidney function of the patient before medication, choosing the appropriate medication according to the patient's age, condition, and comorbidities, and closely detecting the occurrence of the patient's adverse reactions after medication, can avoid serious adverse reactions.

The use of immunosuppressive agents can reduce the use of hormones and prevent the recurrence of the disease.
For SLE patients whose hormone combined with hydroxychloroquine is not effective, or patients who cannot adjust the dose of hormones below a relatively safe dose, immunosuppressive agents are recommended; For those with visceral involvement (lupus nephritis), it is recommended that immunosuppressive agents be added to the initial treatment.

▌Biological agents: SLE patients who have been treated with hormones and/or immunosuppressive agents that are ineffective, intolerant or relapsed, may consider using biological agents for treatment.

For patients with refractory (the effect of conventional treatment is not good) or relapsed SLE, the use of biological agents can significantly increase the patient's complete and partial remission rate, reduce disease activity, disease recurrence rate, and reduce hormone dosage.

At present, only belyumumab (anti-BAFF antibody) has been approved by the U.
S.
Food and Drug Administration (FDA) and the China Food and Drug Administration (CFDA) for the treatment of SLE.

3.
Biological preparations, in the ascendant Figure 2 SLE's new therapeutic target Anti-CD20 antibody: The high allergic-like reaction rate of SLE patients to rituximab seems to be (at least partly) related to the incomplete humanization of rituximab [3].

Many alternative, fully humanized anti-CD20 monoclonal antibodies are under development, such as ocrelizumab and obinutuzumab.

Combination of rituximab and belimumab: B cell depletion through rituximab and belimumab inhibit B cell survival.
The combined application of the two is based on the possibility that the production of BAFF after B cell depletion may promote On the premise of autoreactive B cell maturation [4].

Some clinical trials such as CALIBRATE, SYNBIOSE, BEAT-Lupus reported preliminary data from the study, outlining the efficacy of this strategy.

Anti-CD19 antibody: obexelimab (XmAb5871) is a new type of humanized anti-CD19 antibody with higher affinity for Fcγ receptor ⅡB (FcγRⅡb) [5] and has been used for treatment in a phase Ⅱ clinical trial 104 patients with moderate to severe SLE.

Targeting BTK: Tyrosine protein kinase BTK is expressed by many immune cells, including macrophages, monocytes and B cells, and regulates the downstream signaling pathways of B cell receptors and Fc receptors.

Loss of BTK activity can improve lupus-like diseases in mice, and overexpression of BTK in mouse cells with lupus-like diseases can increase the production of anti-dsDNA antibodies.

Some BTK inhibitors such as ibrutinib and GDC-0853 are undergoing clinical trials to verify their efficacy [6].

CD40-CD40L: CD40-CD40L interaction may be involved in the pathogenesis of SLE.

CD40L is a member of the tumor necrosis factor (TNF) superfamily, and it binds to the receptor CD40 on B cells, leading to B cell differentiation, isotype conversion and the formation of germinal centers [7].

Since CD40-CD40L plays a central role in inducing an immune response, the CD40-CD40L interaction is considered to be an important mechanism for the development of autoimmunity.

In SLE, CD4+ T cells and CD8+ T cells both overexpress CD40L in active diseases, and monocytes and B cells from SLE51 patients also express CD40L abnormally.

In addition, transgenic mice that ectopicly express CD40L on B cells can develop lupus-like diseases.

The results of preclinical studies indicate that inhibition of the CD40-CD40L pathway may help to improve lupus-like diseases.

However, clinical trials of related drugs such as Ruplizumab are not progressing smoothly.

In addition, targeting ICOS-ICOSL, IL-12, IL-23, JAK/STAT pathway, interferon pathway, immune complexes, etc.
are all potential targets for the treatment of SLE.

Summary: In short, SLE is no longer an "immortal cancer".
Early detection, early treatment, and standardized treatment can relieve symptoms, control disease progression, prevent organ involvement, and improve quality of life.

After the physician’s individual customization, the rational application of hydroxychloroquine, glucocorticoids, immunosuppressants and biological agents is the cornerstone of the treatment of diseases.

Current and future biopharmaceuticals may provide additional solutions for a small number of patients who do not respond to standard treatments.

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