Pre-emptive Treatments in Lupus Nephritis Patients With Serological Reactivation

The University of Hong Kong (HKU)

Status: Completed

Conditions: Lupus Nephritis

Treatments: Procedure: Pre-emptive increase of immunosuppressive treatments; Drug: Prednisolone and/or AZA/MMF

Study type: Interventional

Funder types: Other

Identifiers

NCT04870359

UW-16-074

Details and patient eligibility

About

The optimal management of asymptomatic serological reactivation (ASR) in lupus nephritis (LN) patients remained undefined. This project aims to investigate the impact of pre-emptive treatment on disease relapse in LN patients who experienced ASR.

Full description

LN patients who presented with ASR [defined as 1) increase in anti-dsDNA >100 IU/mL , with or without drop in serum complement; or 2) increase in anti-dsDNA to higher than the normal range and >2 times of the preceding value, with or without drop in serum complement; and 3) Absence of renal or systemic manifestations of SLE) will be randomized to receive pre-emptive increase in immunosuppression or had their current immunosuppressive therapies unchanged.

Patients will be followed at 4-, 12-, 24-wk and then every 12 weeks up to 24 months to monitor for renal or extra-renal relapses. Bloods and urine will be collected for measurement of renal and serological parameters, and also B cell signatures.

Primary outcomes: Renal Flare (denoted as proteinuria >1g/D; presence of urinary RBC >30 hpf/RBC casts, or increase in SCr >15% and positive anti-dsDNA)

Secondary outcomes:

• Safety & tolerability of pre-emptive increase of immunosuppressive treatments
• Extra-renal flares
• Renal function at 24 months
• Changes in serological parameters

Enrollment: 49 patients

Sex: All

Ages: 18 to 90 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients with biopsy-proven lupus nephritis who experienced an episode of Asymptomatic Serological Flare (ASF) as defined by:

  1. Increase in anti-dsDNA to >100 IU/mL, with or without drop in serum complement levels OR

  2. Increase in anti-dsDNA to higher than the normal range and more than two times of the preceding value, with or without drop in serum complement levels

     AND

  3. Absence of renal or systemic manifestation of SLE.

Exclusion criteria

1. Patients who cannot provide informed consent.
2. Patients whom the clinicians opined to have excessively high risk of infection or malignancy.
3. Patients who are pregnant or lactating.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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49 participants in 2 patient groups

Pre-emptive Treatment (Prednisolone and/or AZA/MMF)

Active Comparator group

Description:

1. Increase prednisolone to 0.4-0.5 mg/kg/day; taper by 5 mg every 2 weeks to reach 15mg/day; then further reduce by 2.5 mg every 2 week and aim to reach 5-7.5 mg/day after 12 weeks. 2. Adjustment of the 2nd agent would be as follows: 1. For patients who receive AZA \<75mg/day; increase the dose of AZA to 75 mg/day. 2. For patients who receive MMF \<1g/day, increase the dose of MMF to 1g/day.

Treatment:

Drug: Prednisolone and/or AZA/MMF

Procedure: Pre-emptive increase of immunosuppressive treatments

Control

No Intervention group

Description:

Current immunosuppressive regimen and dosage should remain unchanged until the development of renal or extra-renal flares which required increase/change in immunosuppression.