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➤For each increase in SLE disease activity by one unit, patients: the risk of death will increase by 22%; the risk of cardiovascular damage will increase by 17%; the risk of kidney damage will increase by 24%.
➤Using hydroxychloroquine can significantly reduce the risk of death and kidney damage in SLE patients; ➤It is recommended to adopt a more aggressive treatment plan and strictly control disease activity.
Patients with systemic lupus erythematosus (SLE) have diverse clinical manifestations and extensive involvement.
In clinical practice, untimely treatment can easily cause irreversible damage to the affected organs and even death.
In recent years, the mortality rate of SLE patients has decreased significantly, but irreversible organ damage still plagues many patients.
Studies have confirmed that SLE disease activity is an important factor in predicting patient death and organ damage.
Recently, American scholars conducted a cohort study, and the results showed that for every unit of SLE disease activity, the risk of death increases by 22%; the risk of cardiovascular damage increases by 17%; the risk of kidney damage increases by 24%.
Study Design The study included 1168 SLE patients in the Hopkins Lupus cohort who were followed up for ≥24 months (ACR/SLICC classification criteria).
The entire study included: background period (12 months before enrollment in the cohort), observation period (12 months after the background period), and follow-up period (from the end of the observation period to the follow-up period from the end of the observation period to the patient's organ damage/death/loss to follow-up).
The study adjusted the patient’s age, gender, SLE course, hormone use and other factors, and analyzed the correlation between average disease activity and death based on the SLE Disease Activity Index (SELENA-SLEDAI) scoring standard.
The SELENA-SLEDAI scoring standard evaluates 9 organ systems that may be affected by SLE, including 24 scoring rules, with a total score of 105 points.
In patients with SLE International Cooperation Group Injury Index (SDI) = 0, organ damage analysis was performed, and SDI ≥ 1 was defined as damage.
SELENA-SLEDAI and SDI assessments are conducted quarterly.
The demographics of the results showed that the majority of patients (92.
9%) were women.
After correction, in the background period, the mean value of SELENA-SLEDAI of patients was 3, and 54.
9% of patients were in mild-to-moderate disease activity (SELENA-SLEDAI<3); during the observation period and follow-up period, the mean values of SELENA-SLEDAI of patients were both Is 2.
Death was during the follow-up period (median follow-up time was 7 years), and 7.
9% of patients died.
The analysis found that the mean value of SELENA-SLEDAI during the observation period was ≥5, which significantly increased the risk of death during the follow-up period (p<0.
001) (Figure 1).
Figure 1 The relationship between the adjusted SELENA-SLEDAI mean (AMS) and death.
Multivariate analysis shows that every increase of 1 unit in the mean SELENA-SLEDAI during the observation period will significantly increase the risk of death during the follow-up period by 22% (HR=1.
22; 95) %CI: 1.
13~1.
32; p<0.
001); and if the patient used hydroxychloroquine during the observation period, the risk of death during the follow-up period was significantly reduced by 54% (HR=0.
46; 95%CI: 0.
29~0.
72; p<0.
05).
Among the patients without organ damage during the overall organ damage observation period (n=888), 38.
5% of the patients had organ damage during the follow-up period.
Each increase of 1 unit in the mean SELENA-SLEDAI of patients in the observation period significantly increased the risk of organ damage during the follow-up period by 9% (HR=1.
09; 95%CI: 1.
04~1.
15; p<0.
001).
Among the patients with no cardiovascular damage during the observation period for heart, kidney and other organ damage (n=1135), 6.
5% of the patients had cardiovascular damage during the follow-up period. For every increase of 1 unit in the mean SELENA-SLEDAI during the observation period, the risk of cardiovascular injury during the follow-up period increased by 17% (HR=1.
17; 95%CI: 1.
07~1.
29; p<0.
001).
The use of non-steroidal anti-inflammatory drugs (NSAIDs) and antihypertensive drugs during the observation period significantly increased the risk of cardiovascular injury in patients during the follow-up period by 66% (HR=1.
66; 95%CI: 1.
04~2.
63; p<0.
05) and 81%, respectively (HR=1.
81; 95%CI: 1.
09~3.
02; p<0.
05).
In terms of kidney damage, among the patients without kidney damage during the observation period (n=1147), 2.
7% of the patients had kidney damage during the follow-up period.
Every increase of 1 unit in the mean value of SELENA-SLEDAI during the observation period significantly increased the risk of kidney injury during the follow-up period by 24% (HR=1.
24, 95%CI: 1.
08~1.
42; p=0.
003).
The use of hydroxychloroquine during the observation period significantly reduced the risk of kidney damage in patients during the follow-up period by 70% (HR=0.
30; 95%CI: 0.
13 to 0.
68; p<0.
05).
In addition, the mean value of SELENA-SLEDAI during the observation period did not affect the risk of peripheral blood vessel, lung, neuropsychiatric, and musculoskeletal damage.
Discussion and conclusions The results of the study showed that the mean value of SELENA-SLEDAI in SLE patients was significantly correlated with subsequent deaths and organ damage.
For each increase in the mean value of SELENA-SLEDAI by 1 unit, the risk of death in SLE patients increases by 22%; the risk of cardiovascular damage increases by 17%; the risk of kidney damage increases by 24%.
This suggests that SLE patients with stable disease and long-term maintenance of mild-to-moderate disease activity may still experience irreversible organ damage as the disease progresses.
In addition, studies have pointed out that the use of hydroxychloroquine can significantly reduce the risk of death and kidney damage in SLE patients.
This also confirms the recommendation in the guidelines that hydroxychloroquine is recommended for long-term use of hydroxychloroquine as the basic treatment for SLE patients without contraindications.
On the contrary, the use of NSAIDs and antihypertensive drugs will increase the risk of cardiovascular damage, which suggests that these two types of drugs should be used with caution in the SLE population.
In summary, the study revealed that increased SLE disease activity is significantly associated with poor prognosis such as death and organ damage, even in patients with milder disease.
The study emphasized the necessity of strict control of disease activity, and also warned the clinic that more active treatment measures should be taken to control the disease activity of SLE in order to avoid the occurrence and development of poor prognosis.
References: 1.
Hill DD, Eudy AM, Egger PJ, et al.
Impact of systemic lupus erythematosus disease activity, hydroxychloroquine and NSAID on the risk of subsequent organ system damage and death: analysis in a single US medical centre[J].
Lupus Sci Med.
2021 Apr;8(1):e000446.
2.
Bombardier C, Gladman DD, Urowitz MB,et al.
Derivation of the SLEDAI.
A disease activity index for lupus patients.
The Committee on Prognosis Studies in SLE.
Arthritis Rheum.
1992 Jun;35(6):630-40.
➤Using hydroxychloroquine can significantly reduce the risk of death and kidney damage in SLE patients; ➤It is recommended to adopt a more aggressive treatment plan and strictly control disease activity.
Patients with systemic lupus erythematosus (SLE) have diverse clinical manifestations and extensive involvement.
In clinical practice, untimely treatment can easily cause irreversible damage to the affected organs and even death.
In recent years, the mortality rate of SLE patients has decreased significantly, but irreversible organ damage still plagues many patients.
Studies have confirmed that SLE disease activity is an important factor in predicting patient death and organ damage.
Recently, American scholars conducted a cohort study, and the results showed that for every unit of SLE disease activity, the risk of death increases by 22%; the risk of cardiovascular damage increases by 17%; the risk of kidney damage increases by 24%.
Study Design The study included 1168 SLE patients in the Hopkins Lupus cohort who were followed up for ≥24 months (ACR/SLICC classification criteria).
The entire study included: background period (12 months before enrollment in the cohort), observation period (12 months after the background period), and follow-up period (from the end of the observation period to the follow-up period from the end of the observation period to the patient's organ damage/death/loss to follow-up).
The study adjusted the patient’s age, gender, SLE course, hormone use and other factors, and analyzed the correlation between average disease activity and death based on the SLE Disease Activity Index (SELENA-SLEDAI) scoring standard.
The SELENA-SLEDAI scoring standard evaluates 9 organ systems that may be affected by SLE, including 24 scoring rules, with a total score of 105 points.
In patients with SLE International Cooperation Group Injury Index (SDI) = 0, organ damage analysis was performed, and SDI ≥ 1 was defined as damage.
SELENA-SLEDAI and SDI assessments are conducted quarterly.
The demographics of the results showed that the majority of patients (92.
9%) were women.
After correction, in the background period, the mean value of SELENA-SLEDAI of patients was 3, and 54.
9% of patients were in mild-to-moderate disease activity (SELENA-SLEDAI<3); during the observation period and follow-up period, the mean values of SELENA-SLEDAI of patients were both Is 2.
Death was during the follow-up period (median follow-up time was 7 years), and 7.
9% of patients died.
The analysis found that the mean value of SELENA-SLEDAI during the observation period was ≥5, which significantly increased the risk of death during the follow-up period (p<0.
001) (Figure 1).
Figure 1 The relationship between the adjusted SELENA-SLEDAI mean (AMS) and death.
Multivariate analysis shows that every increase of 1 unit in the mean SELENA-SLEDAI during the observation period will significantly increase the risk of death during the follow-up period by 22% (HR=1.
22; 95) %CI: 1.
13~1.
32; p<0.
001); and if the patient used hydroxychloroquine during the observation period, the risk of death during the follow-up period was significantly reduced by 54% (HR=0.
46; 95%CI: 0.
29~0.
72; p<0.
05).
Among the patients without organ damage during the overall organ damage observation period (n=888), 38.
5% of the patients had organ damage during the follow-up period.
Each increase of 1 unit in the mean SELENA-SLEDAI of patients in the observation period significantly increased the risk of organ damage during the follow-up period by 9% (HR=1.
09; 95%CI: 1.
04~1.
15; p<0.
001).
Among the patients with no cardiovascular damage during the observation period for heart, kidney and other organ damage (n=1135), 6.
5% of the patients had cardiovascular damage during the follow-up period. For every increase of 1 unit in the mean SELENA-SLEDAI during the observation period, the risk of cardiovascular injury during the follow-up period increased by 17% (HR=1.
17; 95%CI: 1.
07~1.
29; p<0.
001).
The use of non-steroidal anti-inflammatory drugs (NSAIDs) and antihypertensive drugs during the observation period significantly increased the risk of cardiovascular injury in patients during the follow-up period by 66% (HR=1.
66; 95%CI: 1.
04~2.
63; p<0.
05) and 81%, respectively (HR=1.
81; 95%CI: 1.
09~3.
02; p<0.
05).
In terms of kidney damage, among the patients without kidney damage during the observation period (n=1147), 2.
7% of the patients had kidney damage during the follow-up period.
Every increase of 1 unit in the mean value of SELENA-SLEDAI during the observation period significantly increased the risk of kidney injury during the follow-up period by 24% (HR=1.
24, 95%CI: 1.
08~1.
42; p=0.
003).
The use of hydroxychloroquine during the observation period significantly reduced the risk of kidney damage in patients during the follow-up period by 70% (HR=0.
30; 95%CI: 0.
13 to 0.
68; p<0.
05).
In addition, the mean value of SELENA-SLEDAI during the observation period did not affect the risk of peripheral blood vessel, lung, neuropsychiatric, and musculoskeletal damage.
Discussion and conclusions The results of the study showed that the mean value of SELENA-SLEDAI in SLE patients was significantly correlated with subsequent deaths and organ damage.
For each increase in the mean value of SELENA-SLEDAI by 1 unit, the risk of death in SLE patients increases by 22%; the risk of cardiovascular damage increases by 17%; the risk of kidney damage increases by 24%.
This suggests that SLE patients with stable disease and long-term maintenance of mild-to-moderate disease activity may still experience irreversible organ damage as the disease progresses.
In addition, studies have pointed out that the use of hydroxychloroquine can significantly reduce the risk of death and kidney damage in SLE patients.
This also confirms the recommendation in the guidelines that hydroxychloroquine is recommended for long-term use of hydroxychloroquine as the basic treatment for SLE patients without contraindications.
On the contrary, the use of NSAIDs and antihypertensive drugs will increase the risk of cardiovascular damage, which suggests that these two types of drugs should be used with caution in the SLE population.
In summary, the study revealed that increased SLE disease activity is significantly associated with poor prognosis such as death and organ damage, even in patients with milder disease.
The study emphasized the necessity of strict control of disease activity, and also warned the clinic that more active treatment measures should be taken to control the disease activity of SLE in order to avoid the occurrence and development of poor prognosis.
References: 1.
Hill DD, Eudy AM, Egger PJ, et al.
Impact of systemic lupus erythematosus disease activity, hydroxychloroquine and NSAID on the risk of subsequent organ system damage and death: analysis in a single US medical centre[J].
Lupus Sci Med.
2021 Apr;8(1):e000446.
2.
Bombardier C, Gladman DD, Urowitz MB,et al.
Derivation of the SLEDAI.
A disease activity index for lupus patients.
The Committee on Prognosis Studies in SLE.
Arthritis Rheum.
1992 Jun;35(6):630-40.
