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*Only for medical professionals to read and refer to the latest guidelines for SLE standard treatment! Treatment to target (treat-to-treat, T2T) is a treatment strategy that revolves around preset treatment goals, strictly controls, and adjusts the plan in a timely manner, thereby achieving disease remission
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Over the past 50 years, T2T strategies have played an important role in the clinical application of hypertension, diabetes and rheumatoid arthritis
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Experts and scholars in the field of systemic lupus erythematosus (SLE) have recognized the T2T strategy, but to apply this strategy in clinical practice, more objective and intuitive treatment goals and treatment plans need to be determined
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SLE is a chronic autoimmune disease that can involve systemic systems and organs, and its natural course is often characterized by the alternation of exacerbation and remission of the disease, so that it does not heal.
It is called "immortal cancer"
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With the application of immunosuppressive agents and biological agents such as cyclophosphamide and mycophenolate mofetil, the prognosis of SLE has been greatly improved, but there are still many patients who are in a state of alternating relapse and remission or persistent disease activity for a long time
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Long-term oral administration of low- and medium-dose glucocorticoids, persistent disease activity, and complications such as drug-induced osteoporosis and diabetes are still the reasons for the high mortality of SLE
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This article aims to illustrate how the SLE T2T strategy can help clinicians improve SLE diagnosis and treatment and improve patient outcomes
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History of SLE T2T Strategy Development In 2011, Chinese scholars proposed to introduce T2T strategy in SLE treatment
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In May 2012, the SLE T2T working group was established in Europe to discuss the necessity and feasibility of introducing T2T strategies in SLE, and in June 2014, the world's first SLE T2T recommendation was published
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Several editions of SLE treatment guidelines, such as the "2019 EULAR Updated SLE Treatment Recommendation Guidelines" and "2020 China SLE Diagnosis and Treatment", propose that the T2T strategy runs through SLE treatment
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On January 17, 2022, Prof.
van Vollenho ven RF and others in the Netherlands published a review in Nat Rev Rheumatol to provide guidance for the implementation of SLE T2T
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SLE Disease Activity Evaluation System SLE patients achieving clinical remission or low disease activity status are closely related to long-term prognosis
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So how to evaluate SLE disease activity status? How are disease remission and low disease activity status defined? 1// SLE Disease Activity Index SLE Disease Activity Index 2000 (SLEDAI-2K): At present, SLEDAI-2K is usually used clinically as the scoring standard of lupus activity index
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2// Complete remission is divided into complete remission without serological and clinical activity (SLEDAI-2K=0) and clinical remission with possible serological activity [SLEDAI-2K=4, elevated anti-double-stranded DNA antibody and/or Complement reduction], allowing the use of antimalarial drugs without the use of glucocorticoids and immunosuppressants
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It can also be divided into clinical steroid-free remission (only antimalarial drugs are allowed) and clinical hormonal remission (glucocorticoids and immunosuppressants are allowed, prednisone ≤5mg/d)
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The 2021 Definition of SLE Mitigation (DORIS) Working Group reached a final consensus on the definition of SLE mitigation
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The rules for defining SLE remission include: SLE disease activity index (SLEDAI) = 0 points; patient global assessment index (PGA) < 0.
5 points (standard is 0-3 points); antimalarial drugs, low-dose glucocorticoid doses ≤ 5 mg/d and/or stable doses of immunosuppressants, including biologics
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Although complete remission is the most ideal therapeutic goal in SLE treatment
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However, in clinical practice, complete remission of SLE is actually difficult to achieve, and patients with low disease activity tend to account for a higher proportion
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3// Lupus low disease activity (LLDAS) 1.
SLEDAI-2K≤4 points, no major organ and system involvement (kidney, central nervous system, cardiopulmonary, vasculitis, fever), no hemolytic anemia and gastrointestinal involvement; 2.
Compared with previous assessment, no new lupus activity (based on SLEDAI-2K); 3.
Patient global assessment index (PGA) ≤ 1 point; 4.
Current hormone dosage: prednisone dose (or equivalent dose) ≤ 7.
5mg/d; 5.
Antimalarial drugs, stable doses of immunosuppressants and biological agents can be used
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In recent years, some studies have shown that LLDAS-based therapy can effectively reduce cumulative organ damage and reduce recurrence in patients; DORIS is associated with reduced cumulative organ damage, reduced disease recurrence, and improved HR-QoL
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Finally, given that LLDAS is easier to achieve than DORIS and achieves a similar degree of clinical protection, it helps to reduce organ damage and disease recurrence
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Therefore, LLDAS can be used as a therapeutic target in the target treatment of SLE
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The in-depth study of the pathogenesis of SLE by novel drug therapy to promote SLE T2T strategy provides more potential targets for the development of biologics and small molecule drugs
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Novel drugs have emerged as a promising treatment option in target-targeted therapy, especially in patients who have not responded to conventional treatments
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In patients with SLE and lupus nephritis, the existing new therapeutic drugs include belimumab, rituximab, etc.
targeting B cells; abatacept targeting costimulatory factors; Tocilizumab targeting cytokines Monoclonal antibody; tofacitinib, baricitinib, etc.
targeting small molecules
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In conclusion, T2T strategies are becoming a clinical reality in SLE and are critical for improving outcomes in SLE patients
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There is an international consensus on the two clinical goals of LLDAS and DORIS remission, and their favorable impact on long-term disease outcomes has been validated
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As mentioned in this article, DORIS is the most desirable therapeutic target for SLE, but LLDAS may be a more feasible target than remission for most SLE patients
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Experts and scholars believe that DORIS will become a more realistic and feasible target, while LLDAS may be regarded as an "intermediate target"
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References: [1] Sanchez A, Voskuyl AE, van Vollenhoven R F.
Treat-to-target in systemic lupus erythematosus: advancing towards its implementation [J].
Nat Rev Rheumatol, 2022.
[2] van Vollenhoven RF, Bertsias G , Doria A, et al.
2021 DORIS definition of remission in SLE: final recommendations from an international task force[J].
Lupus Sci Med, 2021,8(1).
[3]Franklyn K, Lau CS, Navarra SV, et al.
al.
Definition and initial validation of a Lupus Low Disease Activity State (LLDAS)[J].
Ann Rheum Dis, 2016,75(9):1615-1621.