In 2011, the author proposed in the Chinese Medical Journal that “the concept of treating to target is needed for SLE”. The concept of treating to target in SLE has been developed, which gives a clear direction and goal to clinical treatment. Once the disease is diagnosed, treatment should be induced toward the goal of complete remission, and even if complete remission cannot be achieved, it should be controlled at a low level of activity as much as possible to prevent the disease from harming the organism. Targeted treatment requires a tight control process to achieve this goal. “Target therapy” is a concept, and “tight control” is the implementation method guided by this concept, and the two are complementary. Since the heterogeneity of SLE and the variability of the disease are much higher than those of RA, the “close control” program for SLE should not be mechanically defined to evaluate the disease once a month and adjust the treatment plan once every three months, as in the case of RA. Rather, the timing of assessment and adjustment of treatment is determined on a case-by-case basis. For example, lupus crisis needs to be evaluated and adjusted at any time; inpatients with severe SLE also need to review all clinical and laboratory indicators within a short period of time; patients discharged from the hospital and those initially treated in outpatient clinics usually need to be reviewed and evaluated every 1-2 weeks in the first month, and monthly thereafter; after the disease is controlled at low activity level, review and evaluate every 3 months; after remission, if the disease is asymptomatic, review and evaluate every 3-6 months. After remission, if the disease is asymptomatic, the assessment can be done every 3~6 months. SLE is a highly heterogeneous disease, with different degrees of severity, urgency, and severity, as well as the patient’s physical condition and sensitivity and tolerance to drugs. Therefore, targeted therapy requires individualization of an initial regimen of induction therapy, and evaluation and adjustment of the regimen during follow-up based on the patient’s response to therapy to ensure progressive improvement of the disease toward the goal of remission or hypoactivity. There is no optimal regimen for induction therapy in SLE, nor is there a right or wrong way to treat it. As long as hormones, slow-acting agents, non-cytotoxic or cytotoxic immunosuppressants are used, it is possible to achieve improvement in the disease. Even for patients with lupus nephritis type IV, most of them will achieve “effective” results with hormones only and no immunosuppressants, including improvement of symptoms, rebound of complement and decrease of proteinuria, etc. Some of them can achieve complete remission. The probability of relapse or fluctuation of disease condition will be lower. It is clear that the treatment of SLE should not only be satisfied with “effective”, but should pursue “better” efficacy under the premise of drug safety. Not only should we pursue complete remission, but we should also make the disease less likely to recur after remission. Hormone is the basic drug for SLE treatment, and the induction treatment plan for SLE needs to be based on hormone. However, the role of hormones is mainly to control active inflammation. During the induction phase of treatment, the usage, dosage and rate of reduction of hormones are mainly determined by the activity of the disease and the degree of inflammatory response. In terms of immunosuppression, the US NIH regimen of intravenous cyclophosphamide (IV-CTX) for lupus nephritis (1,0 g once a month for 6 consecutive doses followed by a maintenance phase) and the European regimen (0,5 g once every 2 weeks for 6 consecutive doses followed by a maintenance phase) may not be fully suitable for Chinese patients. This may be due to the ethnicity, as SLE is heavier in Asian ethnic groups and lighter in Caucasian ethnic groups. Therefore, the IV-CTX regimen more commonly used by the author for the treatment of severe SLE is a dose of 0,4g to 0,6g once a week. For SLE patients with systemic damage but less severe disease that does not require IV-CTX, the author advocates the addition of milder immunosuppressive agents such as morte-macrolimus (MMF) or injectable methotrexate (MTX) rather than hormones only. MMF is close to the US NIH regimen of IV-CTX in terms of efficacy, but not as good as the IV-CTX once weekly regimen. The advantage of MMF is that there is no significant gonadotoxicity. As induction therapy, a starting dose of 2,0 g/d is appropriate for MMF, which is then adjusted appropriately according to efficacy and tolerability. Depending on the intensity of treatment, MTX can be used alone or in combination with cyclosporine A (CsA) or tacrolimus (FK506). both CsA and FK506 are effective drugs for the treatment of SLE, and rapid relapse or rebound of the disease after discontinuation is their main drawback. the author’s experience is to use them in combination with MTX and withdraw CsA or FK506 first after the disease is stabilized, which can ensure This can ensure smooth withdrawal of the drug. As early as around 1990, the treatment paradigm for rheumatoid arthritis changed to step down bridge therapy. After SLE induction therapy, the intensity of treatment began to gradually decrease as the disease improved, which is actually step-down therapy. This is actually step down bridge under tight control. Since the US NIH protocol for lupus nephritis emphasizes: IV-CTX induction therapy once a month, and after 6 consecutive sessions, it is changed to maintenance therapy once every 3 months; the European protocol emphasizes: IV-CTX induction therapy once every 2 weeks, and after 6 consecutive sessions, it is changed to azathioprine or MMF as maintenance therapy. Thus, the global rheumatology community is mostly dogmatically following the 2-stage mindset of induction therapy versus maintenance therapy. In actual clinical practice, however, patients vary greatly on an individual basis. According to the NIH protocol, if after 6 months the patient still has a large amount of proteinuria and the complement is still low, can he or she be moved to the maintenance phase of therapy? If proteinuria disappears after 2 months of treatment and complement returns to normal, is it necessary to continue induction therapy for 4 more months before moving to maintenance therapy? In response to these questions, the author proposed the concept of “individualized treatment of lupus erythematosus based on evidence-based medicine” 10 years ago (Chinese Journal of Internal Medicine, 2004, 43:653). Due to the dogmatic understanding of the “induction therapy and maintenance therapy” model, some controversial questions have arisen in the industry, such as when to move from induction therapy to maintenance therapy for lupus erythematosus? In fact, there is no clear boundary between induction and maintenance treatment for SLE. This is because after SLE treatment, there is no dividing line between the gradual improvement of the disease starting from highly active to complete remission, which is gradual. This is different from the regression after treatment of hematologic tumors, which has a criterion for partial remission and complete remission after treatment, while SLE does not. In the 1980s, the NIH developed the rationale for IV-CTX shock therapy for lupus nephritis, which was modeled after chemotherapy for hematologic neoplasms, giving induction therapy once a month for 6 months and then once every 3 months for 3 years as maintenance therapy. Nowadays, maintenance therapy with IV-CTX every 3 months has been rejected globally, and induction therapy once a month has been rejected by European scholars. We need to rethink IV-CTX shock therapy. Although immune diseases have some similarities with hematologic tumors, immune diseases are not hematologic tumors after all. The author’s experience suggests that the efficacy of immunopathies such as severe SLE and vasculitis is directly related to the dose density of IV-CTX. The dose density of US NIH protocol and European protocol is only 1,0g per month, while the dose density of IV-CTX once a week, if the dose is 0,4g~0,6g, is 1,6g~2,4g per month. increasing the dose density of IV-CTX at the beginning of induction therapy, provided that the patient can tolerate it, can improve the efficacy, shorten the course of the disease, and is more conducive to the early discontinuation of IV- CTX and switching to a less toxic immunosuppressive agent. This will reduce the cumulative dose of IV-CTX and its long-term side effects. Regarding the cumulative dose of IV-CTX for SLE, some scholars once proposed 8g~10g. This is just a general reference for beginners, and you should abandon this dogma when you become a specialist. If SLE is more stubborn and IV-CTX reaches the loading dose of ovarian damage, and the disease has not yet reached the point where the level of immunosuppression can be lowered, stronger alternative regimens including MMF (2,0g/d) or MTX plus CsA or FK506 are needed. We must be clear that as the cumulative dose of IV-CTX increases, the potential toxic side effects increase, especially the risk of gonadal damage and distant tumors. Therefore, we should try to reduce the cumulative dose of IV-CTX and replace IV-CTX with other immunosuppressive agents with fewer side effects once the active lesions of SLE-involved organs improve and complement returns. After IV-CTX, the main immunosuppressive agents that take over are MTX (15 mg/wk), MMF (1,5 g/d), leflunomide (20 mg/ d), azathioprine (50mg~150mg/d), etc. Azathioprine is an immunosuppressant commonly used by western rheumatologists. However, a few Chinese patients have experienced severe bone marrow suppression and baldness as side effects when taking oral azathioprine for about 3 weeks, a side effect rarely reported in the West. The efficacy of MTX for SLE is not yet universally recognized internationally, but it is the author’s experience that once-weekly injections of MTX are superior to azathioprine and have fewer side effects. According to the concept of target therapy, after the treatment of SLE in tight control, some patients can achieve the standard remission, while others have difficulty in achieving complete remission and can only be maintained in a state of low disease activity. The latter undoubtedly requires long-term maintenance with minimal effective doses of drugs. For patients who achieve complete remission, it may be possible to gradually withdraw the hormone or even stop the drug. This brings us to the question “Can SLE be discontinued?” and “What are the consequences of discontinuing SLE? and “What are the indications for stopping SLE?” These are questions that have been debated for years. This is a question that has been debated for many years and has never been answered ideally. Some people believe that the medication can be discontinued, while others advocate lifelong maintenance, “even if half a pill of prednisone is maintained every other day, it will be more reassuring.” This is the view of those who advocate lifelong medication. To answer these questions, we might as well understand the “discontinuation” of SLE as “zero medication”. Because “stopping” can be easily misinterpreted as stopping when the course of treatment is over or when the disease is in complete remission, which is obviously incorrect. Because of this misinterpretation, the question “Can SLE be discontinued? and “What are the indications for stopping SLE?” and so on. And “stopping” can lead to the misconception that the patient is cured and stop the follow-up. Throughout the course of SLE treatment. At the beginning of induction therapy, the intensity of medication may be high, and as the disease improves, the intensity of therapy is gradually reduced. This is referred to as “step-down therapy”: the intensity of medication is gradually reduced as the disease improves to ensure gradual improvement toward the goal of remission or low activity. The sequence is moderate intensity, low intensity, low-low intensity, low-low-low intensity ……, and finally some patients may move to a “zero medication” phase. In fact, the infinite “low” is equal to “zero”, we can understand zero medication as infinite low intensity medication. For example, when the medication is reduced to 2 or 5 mg of oral MTX once a week, the next step is zero medication. The traditional dosing practice for SLE treatment is to “withdraw slow-acting drugs first, then withdraw hormones” after SLE treatment reaches complete remission, i.e., after hormones are only prednisone 10mg/d, slow-acting drugs (including immunosuppressants and hydroxychloroquine) are withdrawn first, and hormones are withdrawn last. However, the author does not agree with this traditional method of drug reduction, but advocates “withdrawing hormones first, then withdrawing slow-acting drugs”. Because small doses of hormones mainly play an anti-inflammatory role, if the SLE with inflammation is still covered by hormones, stopping the slow-acting drugs first will make it difficult to withdraw the hormones. On the contrary, if there is still no indication of inflammatory activity after withdrawing the hormones first, further withdrawal of slow-acting drugs will be smoother. Besides, if SLE is in complete remission and there is no inflammation in the body, it is not justified to continue long-term maintenance hormone use. Therefore, by “withdrawing hormones first and slow-acting drugs later” in the later stages of maintenance therapy, the relapse rate of SLE is lower and a longer period of zero medication use can be obtained. For example, after SLE reaches complete remission, there may be only three drugs left: MTX, prednisone and hydroxychloroquine, commonly known as the MPH regimen. At this point, the author advocates gradually withdrawing the hormones, slowly reducing prednisone from 10 mg/d to 5 mg/d, then to 5 mg every other day, and then stopping the hormones. The withdrawal of MTX and hydroxychloroquine is a slow process, and the patient should be withdrawn first before the withdrawal of hydroxychloroquine if the rash is predominant, or after the withdrawal of MTX if the patient is predominantly suffering from systemic damage. Finally, we can enter the “zero medication” follow-up phase. After “zero medication”, the patient must be followed up every 3 months at first, and then every 6 months if the disease remains in remission. If there are symptoms or disease activity during the “zero medication” follow-up period, the medication must be adjusted promptly. In summary, SLE is a complex and heterogeneous disease, and complete remission and “zero medication” should not be pursued too much in clinical practice. In the process of SLE treatment, any stage and any drug should not be withdrawn or reduced blindly if the disease fluctuates during the withdrawal process. In fact, at present, most SLE patients are still difficult to achieve such an ideal state as “zero medication”. According to the author’s experience, less than half of SLE patients can achieve “zero hormone” after remission, and less than 1/3 of patients can achieve “zero medication”. I hope that the industry will continue to research and explore, so that more SLE patients can achieve long-term complete remission and “zero medication” status.