Does lupus always recur?

*Read only for medical professionals How to prevent lupus recurrence? Systemic lupus erythematosus (SLE) is a hard bone that rheumatologists cannot avoid, and annoying recurrence has become a difficult point in the clinical diagnosis and treatment of SLE
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Countless scholars and doctors have worked hard for it, but it is still difficult to conquer this fortress
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Faced with the recurrence of SLE, Professor Ye Shuang from Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine made a wonderful sharing at the inaugural meeting of the Rheumatology and Immunity Professional Committee of the Chinese Association of Women Physicians in 2022
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The problem of SLE recurrence is actually a pain point for patients.
Due to the long course of SLE, patients will not only experience several recurrences, but also bear the consequences of the accumulation of disease damage
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Since SLE is currently incurable, the disease activity will fluctuate continuously, so the diagnosis and treatment process is also a repeated cycle of "seeing a tall building and seeing it collapse again" until the end of the patient's life
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Professor Ye Shuang pointed out that most of the current SLE clinical studies only focus on the intervention of high disease activity, and few people pay attention to how to delay or even prevent the next recurrence when the disease activity is at the bottom.
This is very important for Professor Ye Shuang and his team.
concerns
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 Figure 1 Map of SLE disease activity After aggregating many clinical studies of SLE, it was found that subjects in observational studies (whether real-world studies or randomized controlled studies) showed that "SLE recurrence is the norm"
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According to studies, the annual recurrence rate of SLE is 7%-32%[1]
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 A study conducted by Prof.
Ye Shuang in 2019 showed that compared with the control group, SLE patients infected with herpes zoster caused an immune disorder with an almost 3-fold increase in the disease recurrence rate (Figure 2).
This study revealed a Hidden data: The annual recurrence rate in SLE patients with low disease activity may be 20%-30%
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Another trial found that antiphospholipid antibody positivity and lack of low disease activity may also be risk factors for SLE recurrence
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 Figure 2 Infection with herpes zoster greatly increases the chance of SLE recurrence [2] To solve the problem of SLE recurrence, this drug can help.
For SLE patients, the current standard treatment strategy requires them to reduce risk exposure when the disease is well controlled, such as Quitting smoking, drinking, etc.
, requires extreme self-discipline in SLE patients
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So, apart from what patients can do, are there any new ways to intervene? That's right, this "magic drug" that may appear in various health issues - metformin is here! Professor Ye Shuang's team found through clinical trials (NCT02741960): SLE patients with low disease activity but high risk of recurrence, combined with metformin therapy, has the potential to reduce disease recurrence, especially major recurrence.
The results were also published in Lancet Rheumatology [3]
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The study enrolled 140 subjects between May 24, 2016, and December 13, 2017, of whom 67 were assigned to the metformin group and 73 were assigned to the placebo group.
At follow-up, the incidence of SLE was not significantly different between 14 (21%) patients in the metformin group and 25 (34%) in the placebo group (RR 0.
68, 95% Cl 0.
42-1.
04, p=0.
078)
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Gastrointestinal adverse events were more frequent in subjects receiving metformin, but the incidence of non-emergent serious adverse events was similar between the two groups, with a significantly lower incidence of infectious events in the metformin group than in the placebo group (p=0.
022 ), no subjects died during the trial; in terms of reducing recurrence, metformin has a protective advantage in reducing major recurrences [4]
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 Figure 3 Intervention effect of metformin on SLE recurrence and other aspects[3] Exploratory analysis showed that, compared with placebo, metformin reduced the incidence of major recurrence by 41% (RR 0.
59) during the 12-month follow-up period (RR 0.
59), This conclusion remains to be confirmed by larger trials
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When Prof.
Ye Shuang analyzed the above study and another study [5] together, he found that metformin reduced disease recurrence in SLE patients with low disease activity, and this effect was stable for serological indicators (anti-double-stranded DNA antibody Negative or normal complement levels) were more pronounced in SLE patients (Fig.
4)
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Figure 4 Survival curve of the effect of metformin on disease recurrence in SLE with low disease activity[6]Summary Most of the current SLE clinical trials focus on how to control active disease, which makes the need for how to prevent recurrence ignored
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However, Professor Ye Shuang sees this issue as the key to linking "active disease control" with "protection from cumulative damage"
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The exploration of metformin makes it possible to become a "good safety and very low cost" secondary prevention option for SLE recurrence
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For patients who have achieved low disease activity, pursuing higher treatment goals, such as glucocorticoid-free DORIS remission, may put them at risk of relapse
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It remains to be explored whether metformin may facilitate the achievement of these higher therapeutic goals in patients with low-activity SLE by preventing relapse
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In previous studies, Professor Ye Shuang's team found that metformin may have a synergistic effect with hydroxychloroquine, which has not been observed with other immunosuppressants (such as mycophenolate mofetil)
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The development of SLE recurrence prevention strategies in the future still requires researchers to continue to work on it
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 Reference [1]Sun F, Chen Y, Wu W, et al.
Varicella zoster virus infections increase the risk of disease flares in patients with SLE: a matched cohort study.
Lupus Sci Med.
2019;6(1):e000339.
Published 2019 Jul 29.
doi:10.
1136/lupus-2019-000339.
[2]Sun F, Chen Y, Wu W, et al.
Varicella zoster virus infections increase the risk of disease flares in patients with SLE: a matched cohort study.
Lupus Sci Med.
2019;6(1):e000339.
Published 2019 Jul 29.
[3]Sun F, Wang HJ, Liu Z, et al.
Safety and efficacy of metformin in systemic lupus erythematosus: a multicentre, randomised, double- blind, placebo-controlled trial[J].
The Lancet Rheumatology, 2020, 2(4): e210-e216.
[4]Petri M, Buyon J, Kim M.
Classification and definition of major flares in SLE clinical trials[J] .
Lupus, 1999, 8(8): 685-691.
[5] Wang H, Li T, Chen S, et al.
Neutrophil extracellular trap mitochondrial DNA and its autoantibody in systemic lupus erythematosus and a proof‐of‐concept trial of metformin[J].
Arthritis & rheumatology, 2015, 67(12): 3190-3200.
[6]Sun F, Geng S, Wang H, et al.
Effects of metformin on disease flares in patients with systemic lupus erythematosus: post hoc analyses from two randomised trials[J].
Lupus science & medicine, 2020, 7(1): e000429.