Low Dosage and Long-Term Use of Cyclophosphamide Improve the Survival of Patients with Systemic Lupus Erythematosus

Abstract Background: Cyclophosphamide (CTX) is an alkylating agent used in the treatment of systemic lupus erythematosus (SLE) for its potent immunosuppression effect. Many aspects of the use of CTX in SLE have been previously studied. However, its relation to mortality in SLE had rarely been mentioned. Thus we investigate the effect of cyclophosphamide on organ involvements and the overall and cause-specific mortality of SLE patients.Methods: Information about CTX prescription were taken from medical records in the Jiangsu Lupus database that was set up to collect data from SLE patients since their first admission during 1999-2009 in Jiangsu province, China. Follow- up studies were carried out in 2010 and 2015 to check the survival status of the patients. Cox regression models were used to estimate hazard ratio (HR) and 95% CI. Kaplan-Meier model was used to assess the effect of CTX on mortality between organ involvements and non-involvements.Results: There were 221 deaths observed out of 2446 SLE patients. CTX users showed a lower mortality of SLE (8.4%) with adjusted HR (95% CI) of 0.74 (0.56-0.97), as compared to non-users. A decreased in overall mortality of SLE in low daily dosage of CTX, with adjusted HR (95% CI) of 0.54 (0.36-0.81) and a significant dose-response pattern (P = 0.004) between overall mortality of SLE and long-term use of CTX with adjusted HR (95% CI) 0.53 (0.35-0.80) were observed. In cause-specific mortality analyses, protective effective of CTX was found to be insignificant. However, CTX could eliminate the differences in mortality between organ involvement and non-involvement, including renal, neuropsychiatric, cardiopulmonary, gastrointestinal and hematological involvements.Conclusion: Low daily dosage and long-term use of CTX lowers the risk of overall mortality of SLE. CTX might improve the survival of patients with renal, neuropsychiatric, cardiopulmonary, gastrointestinal and hematological involvements.

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Seroconversion to antinuclear antibody negativity and its association with disease flare in patients with systemic lupus erythematosus

Lupus ◽

10.1177/0961203320917748 ◽

2020 ◽

Vol 29 (7) ◽

pp. 697-704 ◽

Cited By ~ 1

Author(s):

Oh Chan Kwon ◽

Yong-Gil Kim ◽

Jung Hwan Park ◽

Min-Chan Park

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Antinuclear Antibody ◽

Antinuclear Antibodies ◽

Cox Regression ◽

British Isles ◽

Systemic Lupus ◽

Free Survival ◽

Cox Regression Analysis ◽

Kaplan Meier

Objective To evaluate the rate of seroconversion to antinuclear-antibody negativity in patients with systemic lupus erythematosus and its association with subsequent systemic lupus erythematosus flare risk. Methods Medical records of patients with systemic lupus erythematosus with positive antinuclear antibodies (titer ≥1 : 40) at diagnosis and at least one repeat antinuclear antibody test were reviewed. We determined the frequency of seroconversion to antinuclear antibody negativity among these patients and investigated whether seroconversion to antinuclear antibody negativity was associated with subsequent systemic lupus erythematosus flare risk. The seroconversion to antinuclear antibody negativity was defined as a conversion of positive antinuclear antibodies to a titer below the cut-off of 1 : 40. Systemic lupus erythematosus flare was defined as one new British Isles Lupus Assessment Group A or two new British Isles Lupus Assessment Group B domain scores. To estimate hazard ratios and 95% confidence intervals for systemic lupus erythematosus flare according to seroconversion to antinuclear antibody negativity, Cox regression analysis with adjustment for known systemic lupus erythematosus flare risk factors was performed. Kaplan-Meier analysis was used to compare flare-free survival rates between negative converters and non-converters. Results Among the total 175 patients, seroconversion to antinuclear antibody negativity was found in 17 (9.7%) patients in a median 53.5 (range: 25.7–84.0) months. After the last antinuclear antibody tests, 53 systemic lupus erythematosus flare cases were identified during 14.3 (range: 8.2–21.7) months of follow-up. Systemic lupus erythematosus flare risk was significantly lower in patients with negatively seroconverted antinuclear antibodies (adjusted hazard ratio 0.13, 95% confidence interval 0.03–0.58, p = 0.007). Kaplan-Meier analysis showed significantly higher flare-free survival in negative converters than in non-converters ( p = 0.004). Conclusion Seroconversion to antinuclear antibody negativity occurred in 9.7% of patients over 53.5 months and was associated with a lower future systemic lupus erythematosus flare risk.

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Maternal Systemic Lupus Erythematosus (SLE) High Risk for Preterm Delivery and Not for Long-Term Neurological Morbidity of the Offspring

Journal of Clinical Medicine ◽

10.3390/jcm10132952 ◽

2021 ◽

Vol 10 (13) ◽

pp. 2952

Author(s):

Dora Davidov ◽

Eyal Sheiner ◽

Tamar Wainstock ◽

Shayna Miodownik ◽

Gali Pariente

Keyword(s):

Systemic Lupus Erythematosus ◽

Preterm Delivery ◽

Lupus Erythematosus ◽

Neurological Disease ◽

Cox Model ◽

Perinatal Outcomes ◽

Systemic Lupus ◽

Kaplan Meier ◽

Neurological Morbidity

Objective: Pregnancies of women with systemic lupus erythematosus (SLE) are associated with preterm delivery. As preterm delivery is associated with long-term neurological morbidity, we opted to evaluate the long-term neurologic outcomes of offspring born to mothers with SLE regardless of gestational age. Methods: Perinatal outcomes and long-term neurological disease of children of women with and without SLE during pregnancy were evaluated. Children of women with and without SLE were followed until 18 years of age for neurological diseases. Generalized estimating equation (GEE) models were used to assess perinatal outcomes. To compare cumulative neurological morbidity incidence a Kaplan–Meier survival curve was used, and a Cox proportional hazards model was used to control for confounders. Result: A total of 243,682 deliveries were included, of which 100 (0.041%) were of women with SLE. Using a GEE model, maternal SLE was noted as an independent risk factor for preterm delivery. The cumulative incidence of long-term neurological disease was not found to be significantly higher when using the Kaplan Meier survival curves and maternal SLE was not found to be associated with long-term neurological disease of the offspring when a Cox model was used. Conclusion: Despite the association of SLE with preterm delivery, no difference in long-term neurological disease was found among children of women with or without SLE.

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Systemic Lupus Erythematosus Features in Rheumatoid Arthritis and Their Effect on Overall Mortality

The Journal of Rheumatology ◽

10.3899/jrheum.080091 ◽

2009 ◽

Vol 36 (1) ◽

pp. 50-57 ◽

Cited By ~ 23

Author(s):

MURAT ICEN ◽

PAULO J. NICOLA ◽

HILAL MARADIT-KREMERS ◽

CYNTHIA S. CROWSON ◽

TERRY M. THERNEAU ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Systemic Lupus Erythematosus ◽

Mortality Risk ◽

Lupus Erythematosus ◽

Cox Regression ◽

Systemic Lupus ◽

Risk Of Death ◽

Acr Criteria ◽

Increased Risk ◽

Overall Mortality

ObjectiveFeatures of systemic lupus erythematosus (SLE) are commonly observed in patients with rheumatoid arthritis (RA). However, their frequency and clinical significance are uncertain. We examined the frequency of SLE features in RA and their effect on overall mortality.MethodsWe assembled a population-based incidence cohort of subjects aged ≥ 18 years first diagnosed with RA [1987 American College of Rheumatology (ACR) criteria] between 1955 and 1995. Information regarding disease characteristics, therapy, comorbidities, and SLE features (1982 ACR criteria) were collected from the complete inpatient and outpatient medical records. Cox regression models were used to estimate the mortality risk associated with lupus features.ResultsThe study population comprised 603 subjects with incident RA (mean age 58 yrs, 73% women) with a mean followup time of 15 years. By 25 years after RA incidence, ≥ 4 SLE features were observed in 15.5% of the subjects with RA. After adjustment for age and sex, occurrence of ≥ 4 SLE features was associated with increased overall mortality [hazard ratio (HR) 5.54, 95% confidence interval (CI) 3.59–8.53].With further adjustment for RA characteristics, therapy, and comorbidities, the association weakened but remained statistically significant (HR 2.56, 95% CI 1.60–4.08). After adjustment for age, sex, RA characteristics, therapy, and comorbidities, thrombocytopenia (2.0, 95% CI 1.2, 3.1) and proteinuria (1.8, 95% CI 1.3, 2.6) were significantly associated with mortality.ConclusionSLE features were common in RA, given sufficient observation time. Subjects with RA who developed ≥ 4 SLE features had an increased risk of death. Proteinuria and thrombocytopenia were individually associated with an increased mortality risk.

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Remission in systemic lupus erythematosus: durable remission is rare

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2016-209489 ◽

2016 ◽

Vol 76 (3) ◽

pp. 547-553 ◽

Cited By ~ 41

Author(s):

Theresa R Wilhelm ◽

Laurence S Magder ◽

Michelle Petri

Keyword(s):

Systemic Lupus Erythematosus ◽

Complete Remission ◽

Lupus Erythematosus ◽

Clinical Remission ◽

Cox Regression ◽

Systemic Lupus ◽

High Baseline ◽

Kaplan Meier ◽

Baseline Activity ◽

Major Predictor

IntroductionRemission is the ultimate goal in systemic lupus erythematosus (SLE). In this study, we applied four definitions of remission agreed on by an international collaboration (Definitions of Remission in SLE, DORIS) to a large clinical cohort to estimate rates and predictors of remission.MethodsWe applied the DORIS definitions of Clinical Remission, Complete Remission (requiring negative serologies), Clinical Remission on treatment (ROT) and Complete ROT. 2307 patients entered the cohort from 1987 to 2014 and were seen at least quarterly. Patients not in remission at cohort entry were followed prospectively. We used the Kaplan-Meier approach to estimate the time to remission and the time from remission to relapse. Cox regression was used to identify baseline factors associated with time to remission, adjusting for baseline disease activity and baseline treatment.ResultsThe median time to remission was 8.7, 11.0, 1.8 and 3.1 years for Clinical Remission, Complete Remission, Clinical ROT and Complete ROT, respectively. High baseline treatment was the major predictor of a longer time to remission, followed by high baseline activity. The median duration of remission for all definitions was 3 months. African-American ethnicity, baseline low C3 and baseline haematological activity were associated with longer time to remission for all definitions. Baseline anti-dsDNA and baseline low C4 were associated with longer time to Complete Remission and Complete ROT. Baseline low C4 was also negatively associated with Clinical Remission.ConclusionsOur results provide further insights into the frequency and duration of remission in SLE and call attention to the major role of baseline activity and baseline treatment in predicting remission.

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Long-Term Treatment of the Patient with Systemic Lupus Erythematosus

Nishi Nihon Hifuka ◽

10.2336/nishinihonhifu.37.924 ◽

1975 ◽

Vol 37 (6) ◽

pp. 924-929 ◽

Cited By ~ 1

Author(s):

Hideaki YAMAURA ◽

Masaharu RIKIMARU ◽

Isamu TAKAHASHI ◽

Sadao ANAN ◽

Tomio AKIYAMA ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Term Treatment ◽

Systemic Lupus ◽

Long Term Treatment

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Antiphospholipid syndrome nephropathy in patients with systemic lupus erythematosus and antiphospholipid antibodies: Prevalence, clinical associations, and long-term outcome

Arthritis & Rheumatism ◽

10.1002/art.20433 ◽

2004 ◽

Vol 50 (8) ◽

pp. 2569-2579 ◽

Cited By ~ 152

Author(s):

Maria G. Tektonidou ◽

Flora Sotsiou ◽

Lidia Nakopoulou ◽

Panayiotis G. Vlachoyiannopoulos ◽

Haralampos M. Moutsopoulos

Keyword(s):

Systemic Lupus Erythematosus ◽

Antiphospholipid Syndrome ◽

Lupus Erythematosus ◽

Antiphospholipid Antibodies ◽

Systemic Lupus ◽

Term Outcome ◽

Long Term Outcome ◽

Clinical Associations ◽

Antiphospholipid Syndrome Nephropathy

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Predictors of renal damage in systemic lupus erythematous patients: data from a multiethnic, multinational Latin American lupus cohort (GLADEL)

RMD Open ◽

10.1136/rmdopen-2020-001299 ◽

2020 ◽

Vol 6 (3) ◽

pp. e001299

Author(s):

Cristina Reátegui-Sokolova ◽

Manuel F Ugarte-Gil ◽

Guillermina B Harvey ◽

Daniel Wojdyla ◽

Guillermo J Pons-Estel ◽

...

Keyword(s):

Risk Factors ◽

Systemic Lupus Erythematosus ◽

Latin American ◽

Lupus Erythematosus ◽

Renal Damage ◽

Cox Regression ◽

Damage Index ◽

Early Response ◽

Male Gender ◽

Systemic Lupus

AimA decrease in proteinuria has been considered protective from renal damage in lupus nephritis (LN), but a cut-off point has yet to be established. The aim of this study was to identify the predictors of renal damage in patients with LN and to determine the best cut-off point for a decrease in proteinuria.MethodsWe included patients with LN defined clinically or histologically. Possible predictors of renal damage at the time of LN diagnosis were examined: proteinuria, low complement, anti-double-stranded DNA antibodies, red cell casts, creatinine level, hypertension, renal activity (assessed by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)), prednisone dose, immunosuppressive drugs and antimalarial use. Sociodemographic variables were included at baseline. Proteinuria was assessed at baseline and at 12 months, to determine if early response (proteinuria <0.8 g/day within 12 months since LN diagnosis) is protective of renal damage occurrence. Renal damage was defined as an increase of one or more points in the renal domain of The Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index (SDI). Cox regression models using a backward selection method were performed.ResultsFive hundred and two patients with systemic lupus erythematosus patients were included; 120 patients (23.9%) accrued renal damage during their follow-up. Early response to treatment (HR=0.58), antimalarial use (HR=0.54) and a high SES (HR=0.25) were protective of renal damage occurrence, whereas male gender (HR=1.83), hypertension (HR=1.86) and the renal component of the SLEDAI (HR=2.02) were risk factors for its occurrence.ConclusionsEarly response, antimalarial use and high SES were protective of renal damage, while male gender, hypertension and higher renal activity were risk factors for its occurrence in patients with LN.

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Symptomatic osteonecrosis of the hip and knee in patients with systemic lupus erythematosus: Prevalence, pattern, and comparison of natural course

Lupus ◽

10.1177/09612033211031007 ◽

2021 ◽

pp. 096120332110310

Author(s):

Mehmet Ersin ◽

Mehmet Demirel ◽

Mehmet Ekinci ◽

Lezgin Mert ◽

Çiğdem Çetin ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Rheumatic Diseases ◽

Lupus Erythematosus ◽

Bone Structure ◽

Survival Rates ◽

Knee Joints ◽

Joint Involvement ◽

Systemic Lupus ◽

Kaplan Meier ◽

The Mean

Objective Osteonecrosis (ON), also known as avascular necrosis, is characterized by the collapse of the architectural bone structure secondary to the death of the bone marrow and trabecular bone. Osteonecrosis may accompany many conditions, especially rheumatic diseases. Among rheumatic diseases, osteonecrosis is most commonly associated with systemic lupus erythematosus (SLE). We assessed prevalence and distribution pattern of symptomatic ON in patients with SLE and compare the natural courses of hip and knee ON. Methods 912 SLE patients admitted between 1981 and 2012 were reviewed. SLE patients with symptomatic ON were retrospectively identified both from the existing SLE/APS database. The prevalence of symptomatic ON was calculated; with ON, the joint involvement pattern was determined by examining the distribution of the joints involved, and then the data about the hip and knee joints were entered in the Kaplan-Meier analysis. Kaplan-Meier methods were used to calculate 5- and 10-year rates of ON-related hip (the hip group) and knee survival (the knee group). Results Symptomatic ON developed in various joints in 97 of 912 patients with SLE, and the overall prevalence of ON was detected as 10.6%. The mean age at the time of SLE and ON diagnoses were 27.9 ± 9.9 (14–53) and 34.2 ± 11.3 (16–62) years, respectively. The mean duration from diagnosis of SLE to the first development of ON was 70.7± 60.2 (range = 0–216) months. The most common site for symptomatic ON was the hips (68%, n=66), followed by the knees (38%, n = 37). According to Kaplan-Meier analysis, hip and knee joint survival rates associated with 5-year ON were 51% and 88%, and 10-year survival rates were 43% and 84%, respectively. Conclusion We observed that the prevalence of symptomatic ON in patients with SLE was 10.6%. With the estimated 10-year survival rates of 40% versus 84% for the hip and knee joints, respectively, hip involvement may demonstrate a more aggressive course to end-stage osteoarthritis than the knee involvement.

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