scholarly journals Steady-state mycophenolate mofetil pharmacokinetic parameters enable prediction of systemic lupus erythematosus clinical flares: an observational cohort study

2010 ◽  
Vol 12 (6) ◽  
Author(s):  
Sarah Djabarouti ◽  
Dominique Breilh ◽  
Pierre Duffau ◽  
Estibaliz Lazaro ◽  
Carine Greib ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Cohort Study ◽  
Mycophenolate Mofetil ◽  
Steady State ◽  
Lupus Erythematosus ◽  
Observational Cohort Study ◽  
Pharmacokinetic Parameters ◽  
Systemic Lupus ◽  
Observational Cohort

Early life body size, growth and risks of systemic lupus erythematosus – A large Danish observational cohort study

2020 ◽  
Vol 50 (6) ◽  
pp. 1507-1512 ◽  
Author(s):  
Peter E. Thomas ◽  
Britt W. Jensen ◽  
Kathrine K. Sørensen ◽  
Søren Jacobsen ◽  
Julie Aarestrup ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Cohort Study ◽  
Body Size ◽  
Lupus Erythematosus ◽  
Early Life ◽  
Observational Cohort Study ◽  
Systemic Lupus ◽  
Size Growth ◽  
Observational Cohort

scholarly journals Study protocol for the international Systemic Lupus Erythematosus Prospective Observational Cohort Study (SPOCS): understanding lupus and the role of type I interferon gene signature

BMJ Open ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. e036563
Author(s):  
Edward R Hammond ◽  
Raj Tummala ◽  
Anna Berglind ◽  
Farhat Syed ◽  
Xia Wang ◽  
...  
Keyword(s):  
Cohort Study ◽  
Lupus Erythematosus ◽  
Type I Interferon ◽  
Gene Signature ◽  
Observational Cohort Study ◽  
Type I ◽  
Prospective Observational Cohort Study ◽  
Systemic Lupus ◽  
Observational Cohort ◽  
Interferon Gene

IntroductionThe Systemic Lupus Erythematosus (SLE) Prospective Observational Cohort Study (SPOCS) aims to describe the disease course of SLE and its association with type I interferon gene signature (IFNGS) status.Methods and analysisSPOCS is an international, multicentre, prospective, observational cohort study designed to follow patients through biannual study visits during a 3-year observation period. Patients ≥18 years old with a physician diagnosis that meets the American College of Rheumatology or Systemic Lupus International Collaborating Clinics SLE classification criteria will be included. SPOCS will comprehensively analyse clinical features, disease progression and treatment, SLE outcomes, health status assessments and quality of life, and healthcare resource utilisation of patients with moderate to severe SLE. A four-gene test will be used to measure IFNGS status; scores will be compared with a pre-established cut-off. Patients will be stratified by low or high IFNGS expression levels. Enrolment began in June 2017, and study completion is expected in 2022. The total number of anticipated patients was initially planned for 1500 patients and was amended to 900 patients owing to slow accrual of eligible patients.Ethics and disseminationThe ethics committee/institutional review board/independent ethics committee at each study site approved the SPOCS protocol prior to study initiation (protocol number: D3461R00001, version 3.0, 26 June 2019). Study findings will be disseminated through peer-reviewed publications and presentations at scientific meetings.Trial registration numberNCT03189875.

scholarly journals PK/PD Study of Mycophenolate Mofetil in Children With Systemic Lupus Erythematosus to Inform Model-Based Precision Dosing

2020 ◽  
Vol 11 ◽  
Author(s):  
Yewei Chen ◽  
Li Sun ◽  
Hong Xu ◽  
Min Dong ◽  
Tomoyuki Mizuno ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Logistic Regression ◽  
Mycophenolate Mofetil ◽  
Lupus Erythematosus ◽  
Pediatric Patients ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Data ◽  
Systemic Lupus ◽  
Sledai Score ◽  
Exposure Response

Objectives: To evaluate the mycophenolic acid [MPA, the active form of mycophenolate mofetil (MMF)] pharmacokinetic parameters in relation to clinical response to identify target exposure ranges in pediatric patients with systemic lupus erythematosus (SLE).Methods: This was a retrospective study using pharmacokinetic data collected in 67 pediatric patients aged 4–18 years with SLE. Target MPA exposures for effective inhibition of SLE activity (as measured by SLE disease Activity Index (SLEDAI), active SLE was defined as a SLEDAI score of ≥6, and a controlled disease was defined as a SLEDAI score of ≤4) were assessed by receiver operating characteristic (ROC) curve and logistic regression. Exposure-response models were developed to quantitatively describe the relationship between SLEDAI score and AUC0–12 or Ctrough, respectively.Results: The MPA AUC0-12 in patients with active SLE was significantly lower than that in patients with inactive SLE. ROC analysis revealed that an AUC0–12 threshold of 39 μg h/ml or a Ctrough of 1.01 μg/ml was associated with the lowest risk of active SLE. Logistic regression analysis revealed that an AUC0–12 of less than 34 μg h/ml or a Ctrough of less than 1.2 μg/ml probably is associated with active SLE. The results of the exposure-response modeling also indicated that an AUC0-12 less than 32 μg h/ml or a Ctrough less than 1.1 μg/ml was associated with suboptimal clinical outcome. An AUC0-12 above 50 μg h/ml or a Ctrough above 1.7 ug/ml was associated with disease control.Conclusion: Both AUC0–12 and Ctrough of MPA are predictive of the likelihood of active SLE in pediatric patients receiving MMF. An individualized dosing regimen of MMF, with a target AUC0–12 or Ctrough, should be considered for SLE patients.

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 ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Mycophenolate Mofetil ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Treatment Duration ◽  
Retention Rate ◽  
Renal Involvement ◽  
Joint Involvement ◽  
Systemic Lupus ◽  
Median Treatment

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

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