scholarly journals POS0685 MYCOPHENOLATE MOFETIL IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS: FIVE-YEARS DRUG SURVIVAL IN RENAL AND NON-RENAL INVOLVEMENT

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 588.2-588
Author(s):  
G. Olivieri ◽  
F. Ceccarelli ◽  
F. Natalucci ◽  
F. R. Spinelli ◽  
C. Alessandri ◽  
...  

Background:The updated EULAR recommendations for the management of systemic lupus erythematosus (SLE) underline the use of Mycophenolate Mofetil (MMF) in the treatment of different disease related manifestations (1). Several randomized controlled trials have demonstrated the efficacy of MMF in lupus nephritis (LN) patients but only case series and open-labelled trials have analyzed the use of this drug in other than LN features. Moreover, no data are available about the MMF retention rate in a real-life setting.Objectives:The present study aims at evaluating the 5-years drug retention rate (DRR) of MMF in a large monocentric SLE cohort. Secondly, we investigated the influence of MMF in disease activity changes and chronic damage progression.Methods:We performed a longitudinal study including all the SLE patients (ACR 1997 criteria) starting MMF treatment in our Lupus Clinic. Data about indications, mean dosage, duration of treatment and reasons for drug withdrawal were registered. The DRR was estimated using the Kaplan–Meier method. Disease activity and chronic damage were assessed by SLE Disease Activity Index 2000 (SLEDAI-2K) and SLICC Damage Index (SDI), respectively.Results:The present analysis included 162 SLE patients (M/F 22/140, median age at the disease diagnosis 25.5 years, IQR 13). At the beginning of MMF treatment, we registered a median age of 34 months (IQR 21) and a median disease duration of 72 months (IQR 123). The most frequent indications for prescribing MMF were LN (101 patients, 62.3%) and musculoskeletal manifestations (39, 24.1%), followed by neuropsychiatric involvement (10, 6.2%), and others disease related manifestations (12, 7.4%; in particular skin involvement, hematological features, myositis, vasculitis). MMF was administered at a mean daily dosage of 2.1±0.6 grams; no differences in dosage were found between the different indications (p=ns).At the longitudinal analysis, we registered a median treatment duration of 30 months (IQR 55). Figure 1 reported data about DRR: in particular, at 60 months follow-up we observed a DRR of 61.1% for LN patients, which was similar to that registered for patients without renal involvement (NLN) (60.5%; p=ns). Interestingly, the DRR at 60 months was higher in the subgroup of patients treated for joint involvement (75.4%), even without reaching a statistically significant difference. During the observation period, 92 patients (59.2%) discontinued MMF (median treatment duration at discontinuation 25 months, IQR 35). Interestingly, the main cause of withdrawal was the achievement of persistent remission, observed in 20 patients (21.7%), followed by loss of efficacy (19 patients, 20.5%), drug intolerance and pregnancy planning (17 patients for both reasons, 18,4%). Furthermore, our analysis confirmed MMF efficacy, as demonstrated by the significant reduction in SLEDAI-2k values after 4, 12 and 24 months of treatment (p< 0.0001 for all the time-points in comparison with baseline). In addition, MMF resulted able to control chronic damage progression, as demonstrated by the lack of significant increase in SDI values (baseline: 0.6, IQR 1; last observation: 0.93, IQR 1; p=ns).Conclusion:The evaluation of a large SLE cohort demonstrated a good retention rate for MMF. In particular, our results demonstrated that MMF is also a safe and effective drug for SLE manifestation other than LN, in particular for joint involvement. Moreover, it is able to control disease activity and to prevent the progression of chronic damage.References:[1]Fanouriakis A et al. Ann Rheum Dis. 2019 Jun;78(6):736-745.Disclosure of Interests:None declared

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Conti Fabrizio ◽  
Ceccarelli Fulvia ◽  
Perricone Carlo ◽  
Massaro Laura ◽  
Marocchi Elisa ◽  
...  

Objectives. The anti-dsDNA antibodies are a marker for Systemic Lupus Erythematosus (SLE) and 70–98% of patients test positive. We evaluated the demographic, clinical, laboratory, and therapeutical features of a monocentric SLE cohort according to the anti-dsDNA status.Methods. We identified three groups: anti-dsDNA + (persistent positivity); anti-dsDNA ± (initial positivity and subsequent negativity during disease course); anti-dsDNA − (persistent negativity). Disease activity was assessed by the European Consensus Lupus Activity Measurement (ECLAM).Results. We evaluated 393 patients (anti-dsDNA +: 62.3%; anti-dsDNA ±: 13.3%; anti-dsDNA −: 24.4%). The renal involvement was significantly more frequent in anti-dsDNA + (30.2%), compared with anti-dsDNA ± and anti-dsDNA − (21.1% and 18.7%, resp.;P=0.001). Serositis resulted significantly more frequent in anti-dsDNA − (82.3%) compared to anti-dsDNA + and anti-dsDNA ± (20.8% and 13.4%, resp.;P<0.0001). The reduction of C4 serum levels was identified significantly more frequently in anti-dsDNA + and anti-dsDNA ± (40.0% and 44.2%, resp.) compared with anti-dsDNA − (21.8%,P=0.005). We did not identify significant differences in the mean ECLAM values before and after modification of anti-dsDNA status (P=0.7).Conclusion. Anti-dsDNA status influences the clinical and immunological features of SLE patients. Nonetheless, it does not appear to affect disease activity.


2019 ◽  
Vol 46 (10) ◽  
pp. 1299-1308 ◽  
Author(s):  
Manuel F. Ugarte-Gil ◽  
Daniel Wojdyla ◽  
Guillermo J. Pons-Estel ◽  
Rosana Quintana ◽  
José A. Gómez-Puerta ◽  
...  

Objective.To determine the predictors of remission and low disease activity state (LDAS) in patients with systemic lupus erythematosus (SLE).Methods.Three disease activity states were defined: Remission = SLE Disease Activity Index (SLEDAI) = 0 and prednisone ≤ 5 mg/day and/or immunosuppressants (maintenance dose); LDAS = SLEDAI ≤ 4, prednisone ≤ 7.5 mg/day and/or immunosuppressants (maintenance dose); and non-optimally controlled state = SLEDAI > 4 and/or prednisone > 7.5 mg/day and/or immunosuppressants (induction dose). Antimalarials were allowed in all groups. Patients with at least 2 SLEDAI reported and not optimally controlled at entry were included in these analyses. Outcomes were remission and LDAS. Multivariable Cox regression models (stepwise selection procedure) were performed for remission and for LDAS.Results.Of 1480 patients, 902 were non-optimally controlled at entry; among them, 196 patients achieved remission (21.7%) and 314 achieved LDAS (34.8%). Variables predictive of a higher probability of remission were the absence of mucocutaneous manifestations (HR 1.571, 95% CI 1.064–2.320), absence of renal involvement (HR 1.487, 95% CI 1.067–2.073), and absence of hematologic involvement (HR 1.354, 95% CI 1.005–1.825); the use of immunosuppressive drugs before the baseline visit (HR 1.468, 95% CI 1.025–2.105); and a lower SLEDAI score at entry (HR 1.028, 95% CI 1.006–1.051 per 1-unit decrease). These variables were predictive of LDAS: older age at entry, per 5-year increase (HR 1.050, 95% CI 1.004–1.098); absence of mucocutaneous manifestations (HR 1.401, 95% CI 1.016–1.930) and renal involvement (HR 1.344, 95% CI 1.049–1.721); and lower SLEDAI score at entry (HR 1.025, 95% CI 1.009–1.042).Conclusion.Absence of mucocutaneous, renal, and hematologic involvement, use of immunosuppressive drugs, and lower disease activity early in the course of the disease were predictive of remission in patients with SLE; older age was predictive of LDAS.


Lupus ◽  
2019 ◽  
Vol 28 (3) ◽  
pp. 383-388
Author(s):  
F Ceccarelli ◽  
C Perricone ◽  
E Cipriano ◽  
L Massaro ◽  
F Natalucci ◽  
...  

Specific indices are not available to evaluate systemic lupus erythematosus (SLE) joint involvement; indeed, the application of indices validated for rheumatoid arthritis has been suggested. We evaluated the usefulness of organ specific composite indices, i.e. the Disease Activity Score on 28 joints (DAS28), Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), and the ratio of swollen to tender joints (STR), to assess SLE joint activity by analyzing the correlation between these indices and ultrasonography (US) inflammatory status. We evaluated SLE patients with arthralgia and/or arthritis: the above-mentioned indices were calculated and the SLE Disease Activity Index 2000 (SLEDAI-2k) was applied to assess global disease activity. US of I–V metacarpophalangeal, I–V proximal interphalangeal, wrist, and knee bilateral was performed. Synovial effusion/hypertrophy and power Doppler findings were scored according to a semi-quantitative scale (0–3) to obtain an inflammatory total score (0–216). One hundred and six patients (M/F 7/99, median age 49.5 years (IQR 17.0), median disease duration 8.5 years (IQR 17.0)) were enrolled. We identified a positive correlation between US score and DAS28-CRP ( r = 0.3, p = 0.007), STR ( r = 0.42, p = 0.0005), SDAI ( r = 0.33, p = 0.02), CDAI ( r = 0.29, p = 0.03); US score reflected different levels of clinimetric joint activity. In conclusion, we suggest the ability of composite indices in detecting SLE joint inflammation and their possible real-life use.


2016 ◽  
Vol 25 (1) ◽  
pp. 27-36
Author(s):  
Alina Dima ◽  
◽  
Camelia Badea ◽  
Eugenia Balanescu ◽  
Simona Caraiola ◽  
...  

Introduction. Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of unknown origins with increasing prevalence worldwide. Lupus clinical and immunological features are complex and heterogeneous, but peculiar characteristics in different population were described. Aim. Description of specific clinical and biological features of SLE patients. Methods. 134 patients fulfilling the 2012 SLE Systemic Lupus International Collaborating Clinic criteria were enrolled. Baseline characteristics and biological features (such as sex, age, age at disease onset, disease duration, tobacco and alcohol habits, cardiovascular and fracture risk factors) were collected in all consenting patients prospectively included. Also, disease activity scores such as Systemic Lupus Activity Measure (SLAM), European Consensus Lupus Activity Measurement, Systemic Lupus Erythematosus Disease Activity Index, and accrual damage Systemic Lupus International Collaborating Clinics/American College of Rheumatology index were assessed when data needed for these scores were available. Results. A number of 134 SLE patients, majority of feminine sex (89.6%) were enrolled. The mean ± SD age at inclusion and onset age were 46.4 ± 12.9 years and 36.5 ± 12.2 years. 19.4% of patients included were current smokers. Regarding comorbidities, 8.5% associated diabetes and 41.8% hypertension. Anti-deoxyribonucleic acid antibodies were identified in the antecedents of only 50.4% of the searched cases; higher proportion of positivity was found for lupus anticoagulant, respectively 70.9%. Joint involvement was the most frequent clinical criterion used to sustain the lupus diagnosis (110 patients, 82.1%), while the hematological one the most frequent involvement at inclusion (50 patients, 37.3%). 67.9% of patients presented SLAM score results less or equal to 5 points, 10.4% results between 5 and 8 points, and 21.6% of more or equal to 8 points. The majority of patients enrolled were under corticosteroid treatment (109 patients, 81.3%) and also an important part was receiving Hydroxychloroquine (108 patients, 80.6%). Conclusion. In this cross-sectional study, we presented important data related to general characteristics, biological parameters, immunological features, disease scores, and treatment principles in a single-center sample of SLE patients.


Lupus ◽  
2020 ◽  
Vol 29 (3) ◽  
pp. 239-247 ◽  
Author(s):  
Y Li ◽  
R Jia ◽  
Y Liu ◽  
S Tang ◽  
X Ma ◽  
...  

Objectives Antibodies against carbamylated protein (anti-CarP) were found to be a promising marker to evaluate joint damage and disease activity in patients with rheumatoid arthritis (RA). However, whether anti-CarP antibodies were present in systemic lupus erythematosus (SLE) remained ambiguous. We have therefore undertaken this study to assess the levels of serum anti-CarP antibodies and to evaluate their clinical value in SLE. Methods Serum levels of antibodies against carbamylated-vimentin (anti-Carp) were measured by enzyme immunosorbent assay in 100 patients with SLE, 76 with RA, 17 with primary Sjögren syndrome (pSS), and 68 healthy controls. Data analyses between anti-Carp antibodies and other laboratory measures were performed using SPSS 24 software for Windows. Results The levels of serum anti-CarP antibodies in patients with SLE were significantly higher than those in healthy controls. In addition, anti-CarP antibodies were present in SLE patients lacking the disease-specific antibodies, including anti-Smith–negative patients (24.4%, 21/86), anti-dsDNA–negative patients (29.3%, 12/41), anti-nucleosome–negative patients (21.4%, 9/42), and antiribosomal P protein antibody–negative patients (23.7%, 18/76). There were significant differences between the anti-CarP–positive and anti-CarP–negative SLE patients in clinical and laboratory features, such as age, erythrocyte sedimentation rate (ESR), C-reactive protein, rheumatoid factor, third-generation cyclic citrullinated peptide (CCP3), anticardiolipin, D-dipolymer, complement 3, immunoglobulin G (IgG), red blood cell count (RBC) and hemoglobin. After adjusting for age and disease duration, the high levels of anti-CarP antibodies were still correlated with low RBC, hemoglobin and high ESR, IgG and CCP3. Active SLE patients demonstrated higher anti-CarP IgG than inactive patients. Moreover, the levels of anti-CarP were significantly higher in SLE patients with arthralgia and/or arthritis than in those without joint involvement. Conclusions Anti-CarP antibodies were present in SLE patients and associated with the disease severity. These might provide a potential supplement to other specific autoantibodies for diagnosis of SLE and serve as a promising marker for measuring joint damage in the disease.


Lupus ◽  
2019 ◽  
Vol 28 (7) ◽  
pp. 826-833 ◽  
Author(s):  
R Wakiya ◽  
T Kameda ◽  
K Ueeda ◽  
S Nakashima ◽  
H Shimada ◽  
...  

Objectives We investigated the effect of hydroxychloroquine (HCQ) on S100A8 and S100A9 serum levels in systemic lupus erythematosus (SLE) patients with low disease activity receiving immunosuppressants. Methods SELENA-SLEDAI, Cutaneous Lupus Erythematous Disease Area and Severity Index (CLASI) and serum levels of complement factors, anti-dsDNA antibodies, and white blood cell, lymphocyte, and platelet counts were used to evaluate disease activity, cutaneous disease activity, and immunological activity, respectively. Serum S100A8 and S100A9 were measured at HCQ administration and after 3 or 6 months using ELISA. Results S100A8 and S100A9 serum levels were elevated at baseline and the magnitude of decrease from baseline at 3 and 6 months after HCQ administration was greater in patients with renal involvement than in those without (baseline: S100A8, p = 0.034; S100A9, p = 0.0084; decrease: S100A8, p = 0.049; S100A9, p = 0.023). S100 modulation was observed in patients with ( n = 17; S100A8, p = 0.0011; S100A9, p = 0.0002) and without renal involvement ( n = 20; S100A8, p = 0.0056; S100A9, p = 0.0012), and was more apparent in patients with improved CLASI activity scores (improved: S100A8, p = 0.013; S100A9, p = 0.0032; unimproved: S100A8, p = 0.055; S100A9, p = 0.055). No associations were observed for immunological biomarkers. Conclusion HCQ may improve organ involvement in SLE by modulating S100 protein levels, especially in patients with renal or skin involvement.


2005 ◽  
Vol 12 (1) ◽  
pp. 56-59 ◽  
Author(s):  
Krisztina Sallai ◽  
Eszter Nagy ◽  
Beata Derfalvy ◽  
Györgyi Müzes ◽  
Peter Gergely

ABSTRACT Nucleosomes are the dominant autoantigens in patients with systemic lupus erythematosus (SLE), and immune complexes involving nucleosomes are the major cause of tissue damage. The activity of DNase I, the enzyme responsible for nucleosome degradation, has been found to be decreased in patients with SLE. However, it is not known whether DNase activity is a clinically useful parameter. The aim of our study was to assess DNase activity in a prospective study of 113 patients with SLE in relation to disease activity and organ involvement. We included two control groups: 9 patients with undifferentiated connective tissue disease (UCTD) and 14 healthy individuals. DNase activity was found to be lower in patients with SLE (63.75% ± 12.1%) than in the controls (81.3% ± 9.25%) (P < 0.001). DNase activity in patients with UCTD (64.9% ± 18.2%; P = 0.854) did not differ from that in patients with SLE. Patients with SLE had higher antinucleosome antibody titers (356.3 ± 851) than the controls (1.44 ± 2.77; P < 0.01) or UCTD patients (39.9 ± 57.7; P < 0.01). In addition, samples positive for antinucleosome antibodies displayed low levels of DNase activity. Within the SLE group, the presence of renal disease had no impact on DNase activity or antinucleosome antibody titers. Also, the SLE disease activity index showed no correlation with DNase activity. In a longitudinal study of six SLE patients, DNase activity did not follow disease activity or autoantibody titers. Our results confirm that serum DNase activity is decreased in patients with SLE, but we conclude that it is not a clinically useful parameter for the prediction of flare-ups of disease or renal involvement.


2016 ◽  
Vol 43 (3) ◽  
pp. 565-575 ◽  
Author(s):  
XiangYang Huang ◽  
Laurence S. Magder ◽  
Michelle Petri

Objective.The risk factors for incident seizures in systemic lupus erythematosus (SLE) were prospectively determined in a cohort study.Methods.A total of 2203 patients with SLE followed longitudinally in the Hopkins Lupus Cohort were analyzed. Demographic variables, clinical manifestations, laboratory tests, and SLE disease activity were recorded at each quarterly visit. Adjusted estimates of association of risk factors for onset of seizure were derived using pooled logistic regression. We examined incident seizures in 3 ways: at the time of diagnosis, more than 45 days after the diagnosis of SLE, and after cohort entry.Results.Of 2203 patients with no history of seizure prior to SLE diagnosis, 157 (7.13%) had the first seizure occurrence at the time of (37 patients, 1.68%) or after diagnosis (120 patients, 5.45%) of SLE. The risk of seizure occurring around the time of SLE diagnosis was higher in patients with a history of malar rash (p = 0.002), proteinuria (p = 0.004), and psychosis (p < 0.001). Multivariable analysis of the first seizure occurring after the diagnosis of SLE showed that history of low C3 (p = 0.0078), psychosis (p < 0.0001), cranial or peripheral neuropathy (p = 0.0043), anti-Sm antibody (p = 0.0551), renal involvement (p = 0.0177), and current corticosteroid dose (p < 0.0001) were independently associated with a higher incidence of seizure. Disease activity was not predictive after adjusting for corticosteroids.Conclusion.Risk of seizure after diagnosis of SLE is increased in those patients with prior psychosis, neuropathy, proteinuria, anti-Sm, low C3, and use of corticosteroids.


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