Therapeutic Drug Monitoring of Mycophenolate Mofetil in Lupus Nephritis (LUPUS-MONITOR)

Impact of Therapeutic Drug Monitoring of Mycophenolate Mofetil in Patients With Lupus Nephritis: A Randomized Clinical Trial

Systemic lupus erythematosus (SLE) is an inflammatory, chronic, and multisystem autoimmune disease characterized by periods of activity and remission. Lupus nephritis (LN) is the most frequent renal complication and is associated with high morbidity, manifesting as nephritic or nephrotic syndrome, complement consumption, and positivity for anti-double-stranded DNA antibodies.

Mycophenolate mofetil (MMF) is an immunosuppressive agent that modifies the course of LN and is converted into mycophenolic acid (MPA), its measurable active metabolite. However, MMF exhibits complex interindividual and interethnic variability in metabolism, reinforcing the need for personalized strategies through therapeutic drug monitoring (TDM) to ensure renal remission.

The objective of this study is to determine whether the implementation of MPA TDM results in a higher rate of renal remission over 12 months compared with standard treatment.

This is a randomized, blinded clinical trial to be conducted at a teaching hospital in Maranhão over a 12-month period. From an estimated population of 187 eligible patients with LN receiving MMF, 100 consecutive participants will be randomized (50 per group).

MPA monitoring will occur at three time points (T1, T2, T5), while clinical and laboratory outcome assessments will be performed quarterly (T1-T5). The primary outcome will be the renal remission rate; secondary outcomes include serum MPA levels, adverse events, hospitalizations, and medication adherence.

This study will generate evidence on precision therapeutics applied to MMF in LN within the Brazilian public health system (SUS), particularly regarding the pilot use of TDM for dose optimization and maximization of clinical response.

Study Overview

• Status: Not yet recruiting
• Conditions: Systemic Lupus Erythematosus; Lupus Nephritis; Drug Monitoring; Mycophenolic Acid
• Intervention / Treatment: Other: Therapeutic Drug Monitoring; Other: Standard clinical care

Detailed Description

Randomized clinical trial, blinded to participants, to be conducted with patients treated at the Rheumatology Outpatient Clinic of the University Hospital of the Federal University of Maranhão (HU-UFMA) by a clinical pharmacist/researcher from the Clinical Pharmacy Unit (UFCLI) and a rheumatologist. The Clinical Research Center (CEPEC/UFMA) and the Clinical Analysis Laboratory of HU-UFMA will serve as reference sites for patient blood collection and for performing and analyzing laboratory tests, respectively. Serum MPA levels will be measured by a reference laboratory. The study will be conducted with patients diagnosed with lupus nephritis who are receiving mycophenolate mofetil through the Specialized Component of Pharmaceutical Services of the Brazilian Public Health System (SUS), over a 12-month period.

General objective is determine whether the implementation of therapeutic drug monitoring of mycophenolate mofetil (TDM-guided) in patients with lupus nephritis results in a higher rate of renal remission over 12 months compared to standard clinical management.

Specific objectives is to evaluate secondary clinical outcomes of lupus nephritis (LN), such as the rate of patients achieving renal remission, partial remission and relapse rates, rate of non-response, number of dose adjustments, and mean MMF dose adjusted over 12 months. To determine the association between C0 concentration and reduction in proteinuria/estimated Glomerular Filtration Rate (eGFR), as well as adverse events. To determine the occurrence of adverse effects, hospitalizations, rate of temporary or permanent MMF discontinuation due to toxicity, and medication adherence.

To evaluate the impact of the clinical pharmacist's role in the MMF dose adjustment process guided by TDM, considering dose appropriateness, achievement of the target therapeutic range, and patients' clinical outcomes, in addition to promoting health education and treatment adherence.

Based on clinical records from HU-UFMA and FEME/MA, it is estimated that approximately 187 patients diagnosed with lupus nephritis (classes III-V) and receiving mycophenolate mofetil (MMF) are currently under specialized outpatient follow-up. However, according to the sample size calculation described below, 50 participants will be required in each group, totaling 100 randomized patients (control group and intervention group). The sample will consist of consecutive patients who meet the eligibility criteria and agree to participate by signing the informed consent form. Recruitment will occur continuously until the established sample size is reached.

The sample size calculation was based on comparing the proportion of patients achieving renal remission at 12 months in the control group (MMF with usual management) versus the intervention group (MMF with therapeutic drug monitoring of mycophenolic acid [MPA] and dose adjustment guided by TDM). A remission rate of 60% was assumed for the control group and 80% for the intervention group, resulting in an expected difference of 20 percentage points between proportions.

Assuming a significance level of 10% (α = 0.10) and statistical power of 70% (β = 0.30), the minimum required sample size was 49 participants per group, calculated using the formula for comparison of two independent proportions. To account for potential losses to follow-up (up to 10%) and ensure robustness of the analysis, the value was rounded up to 50 participants per group, totaling 100 patients.

As this is a single-center, randomized clinical trial with an exploratory design, the sample parameters were defined considering operational feasibility and focusing on generating estimates to support future multicenter studies with greater statistical power.

Eligible participants will include adults aged 18 years or older, of both sexes, followed at the rheumatology outpatient clinic with a diagnosis of systemic lupus erythematosus (SLE), and active lupus nephritis (class III-V) documented by renal biopsy with histological classification within the past six months or by proteinuria defined as protein-to-creatinine ratio (PCR) > 0.5 or 24-hour proteinuria > 500 mg, while receiving MMF during the maintenance phase within the first three months.

Individuals with contraindications to MMF (known hypersensitivity, pregnancy, or breastfeeding), active severe infection (e.g., tuberculosis or sepsis), unstable renal replacement therapy, severe hepatic impairment, use of investigational drugs, or concomitant use of medications that strongly alter pharmacokinetics (PK) without the possibility of adjustment (e.g., rifampin) will be excluded.

Participants will be recruited through the electronic medical record system (AGHUx) to identify patients followed at the rheumatology outpatient clinic at HU-UFMA, as well as through reports of patients receiving MMF dispensed by the Specialized Medication Pharmacy (FEME) of the State of Maranhão between January 2026 and December 2027.

Randomization: Participants will be randomly assigned (1:1) in blocks of four to receive either TDM-guided MMF therapy or standard MMF treatment. An independent researcher will perform group allocation and generate the randomization sequence using a computer-based algorithm. Observers will be blinded to group allocation through the use of sealed, opaque envelopes to ensure allocation concealment. Data analysts will not be involved in participant assessment or treatment and will remain blinded to group allocation until the data analysis phase.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Elayne E Costa da Silva; Phone Number: +55 98 21091280; Email: costa.elayne@gmail.com

Study Locations

• Brazil
  • Maranhão
    • São Luís, Maranhão, Brazil, 65020-070
      • University Hospital of the Federal University of Maranhão
      • Contact: Elayne Costa da Silva; Phone Number: +55982109-1280; Email: elayne.silva@huufma.br
      • Principal Investigator: Elayne Costa
      • Sub-Investigator: Rodrigo Mendonça
      • Sub-Investigator: Vanessa Bergamin
      • Sub-Investigator: Andrea Fontenelle

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

• Adults aged ≥18 years, of both sexes
• Diagnosis of systemic lupus erythematosus (SLE) according to the ACR criteria, with at least four criteria present for the diagnosis of SLE, and active lupus nephritis (class III-V) documented by renal biopsy with histological classification within the last 6 months or presence of urine protein-to-creatinine ratio (UPCR > 0.5) or 24-hour proteinuria (>500 mg)
• Use of mycophenolate mofetil (MMF) in the maintenance phase within the first 3 months
• Residents of the municipalities of São Luís, São José de Ribamar, and Paço do Lumiar, located in the Metropolitan Region of Greater São Luís

Exclusion criteria:

• Individuals with contraindications to MMF (known hypersensitivity, pregnancy, or breastfeeding)
• Active severe infection (e.g., tuberculosis, sepsis)
• Unstable renal replacement therapy and severe hepatic failure
• Use of investigational drugs
• Concomitant use of drugs that strongly modify pharmacokinetics (PK) without the possibility of adjustment, such as rifampicin.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TDM-guided; Serum MPA (C0) measurement will be performed at three time points (T1, T2, and T5). Between these visits, outpatient clinical evaluations (T1 to T5) will be conducted without bioanalytical MPA collection, allowing continuous clinical follow-up with reduced participant burden and optimized resource use. Will be evaluated complete clinical remission of lupus nephritis (LN) or target renal response, partial clinical remission of LN, and lack of response, measured by 24-hour proteinuria and urinary protein-to-creatinine ratio e MPA concentration (C0) throughout follow-up (T1, T2, T5), Adverse events related to MMF, Hospitalizations related to lupus nephritis and Medication adherence.	Other: Therapeutic Drug Monitoring; The serum MPA (C0) concentration will be measured at three time points (T1, T2, and T5). Between these visits, outpatient clinical assessments (T1 and T5) will be conducted without bioanalytical MPA sampling, allowing for continuous clinical follow-up with reduced participant burden and optimized resource utilization
Active Comparator: Control group; Participants will receive MMF according to the Brazilian Ministry of Health protocol for lupus nephritis, with quarterly clinical evaluations (T1-T5) and no therapeutic drug monitoring of MPA. Will be evaluated complete clinical remission of lupus nephritis (LN) or target renal response, partial clinical remission of LN, and lack of response, measured by 24-hour proteinuria and urinary protein-to-creatinine ratio e MPA concentration (C0) throughout follow-up (T1, T2, T5), Adverse events related to MMF, Hospitalizations related to lupus nephritis and Medication adherence.	Other: Standard clinical care; The participant will be receiving MMF according to the Ministry of Health protocol for lupus nephritis, with quarterly clinical assessments (T1-T5) conducted without therapeutic drug monitoring of MPA.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of patients in renal remission	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Trough MPA concentration (C0) over follow-up	Trough MPA concentration (C0)	12 months
adverse events	MMF-related adverse events	12 months
hospitalizations	Lupus nephritis-related hospitalizations	12 months
Medication adherence	Medication adherence (Brief Medication Questionnaire - BMQ) Adherent: patient with no positive responses in the three domains of the questionnaire (score = 0/ Adherent: BMQ = 0) Non-adherent (low adherence): ≥3 positive responses, indicating multiple barriers to the correct use of medications (BMQ ≥ 1).	12 months

Collaborators and Investigators

• Sponsor: Federal University of Maranhao
• Collaborators: Universidade Federal de Alfenas

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: March 11, 2026
• First Submitted That Met QC Criteria: March 23, 2026
• First Posted (Actual): March 25, 2026

Study Record Updates

• Last Update Posted (Actual): March 25, 2026
• Last Update Submitted That Met QC Criteria: March 23, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Glomerulonephritis; Nephritis; Skin and Connective Tissue Diseases; Lupus Erythematosus, Systemic; Lupus Nephritis
• Other Study ID Numbers: 94827126.0.0000.5086

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No