Initial phase (0–12 months)
The initial phase of the treatment (0–12 months) will comprise standard of care immunosuppressive therapy according to current recommendations, i.e. MMF or Euro-Lupus IV CYC as described below, as well as antimalarial and antiproteinuric/renoprotective therapy unless contraindicated [Fanouriakis A. et al. Ann Rheum Dis. 2020]. Regimens may include add-on therapies, e.g. clinical trial drugs if the interventional part of the clinical trial lasts for 12 months or less and, thus, does not interfere with the protocol of ReBioLup.
- Initial treatment: Mycophenolate mofetil equivalent dose 2–3 g/day (6 months).
- Subsequent treatment: Mycophenolate mofetil equivalent dose 1–2 g/day (3–5 years).
Euro-Lupus IV CYC regimen
- Initial treatment: IV cyclophosphamide pulses of 500 mg biweekly (6 pulses).
- Subsequent treatment: Azathioprine 2 mg/kg/day (3–5 years) or mycophenolate mofetil equivalent dose 1–2 g/day (3–5 years).
- Initial treatment:
- Intravenous pulses of methylprednisolone (total dose of 500–2500 mg).
- Oral prednisone or equivalent 0.3–0.5 mg/kg/day tapered to ≤ 5–10 mg/day by 3–6 months.
- Subsequent treatment: The lowest possible dose needed (steered by the treating physician).
Antimalarial agents should be used unless contraindicated
- Hydroxychloroquine 5 mg/kg/day; one daily intake.
- Chloroquine phosphate 160 mg/day.
- ACE inhibitors and/or ARBs (maximal tolerated dose).
- Annual influenza vaccination.
- Anti-pneumococcal vaccination.
- Calcium and vitamin D3 supplements.
- Statins if needed.
- Low molecular weight heparin if serum albumin < 20 g/L.
- As per standard of care recommendations.
Treatment after repeat kidney biopsy (from 12 months onwards)
For patients with 2003 ISN/RPS class III/IV (± V) LN at baseline:
- If NIH activity index score ≤ 3: the immunosuppressive treatment remains unchanged.
- If NIH activity index score > 3: check for and record non-adherence (as per good clinical practice, e.g. questionnaires, discussion with the patients, determination of hydroxychloroquine levels), and intensify the immunosuppression, utilising one or several of the following options.
- Stimulate adherence.
- Increase glucocorticoids (oral glucocorticoids or IV methylprednisolone).
- Increase dose of immunosuppressive agent.
- Switch from MMF to AZA or from AZA to MMF.
- Add-on IV CYC.
- Add-on calcineurin inhibitors.
- Switch to rituximab.
- Switch to (or add) new available therapeutic modalities.
For patients with 2003 ISN/RPS class V LN, individual assessment of the repeat biopsy should steer the decision of treatment at the respective site. Results from this study will generate data on how to evaluate response to therapy in pure membranous LN, as well as the value of the information retrieved from repeat kidney biopsies in portending long-term renal prognosis.