Therapeutic Drug Monitoring of Mycophenolate Mofetil in Lupus Nephritis

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.