Trial of Rituximab and Mycophenolate Mofetil Without Oral Steroids for Lupus Nephritis

1. Adults aged 18-75 years old and children aged 12-17 years old.

2. Active lupus nephritis, as defined by kidney biopsy within prior 8 weeks assessed bythe International Society of Nephrology/Renal Pathology Society (ISN/RPS)classification:

3. class III (A or A/C) with active lesions in at least 20% of the viable glomeruli,or

4. class IV-S (A or A/C) with active lesions in at least 20% of the viableglomeruli, or

5. class IV-G (A or A/C) with active lesions in at least 20% of the viable glomeruliand / or

6. class V and

7. urine protein-to-creatinine ratio equal to or greater than 100mg/mmol (>1mg/mg )at randomisation or at any time within 28 days before randomisation

8. No contraindications to the use of IV methyl prednisolone, MMF, oral steroids orrituximab or any other required medications such as antipyretics, antihistamines

9. Ability to provide informed consent

10. As MMF is teratogenic and on basis of advice from NHS England (The updatedrecommendations (https://www.gov.uk/drug-safety-update/mycophenolate-mofetil-mycophenolic-acid-new-pregnancy-prevention-advice-for-women-and-men) for patients whilst on MMF and afterstopping are:

• Women who have child bearing potential should be willing to use 2 forms ofeffective contraception during treatment and for 6 weeks after stopping treatment

• Men (including those who have had a vasectomy) should be willing to use condomsduring treatment and for at least 90 days after stopping treatment. This adviceis a precautionary measure due to the genotoxicity of these products

• Female partners of male patients treated with mycophenolate mofetil should usehighly effective contraception during treatment and for 90 days after the lastdose

Exclusion criteria:

1. Obsolescence of >50% of the glomeruli or tubulointerstitial scarring of >50% orcellular crescents in >50% of the glomeruli

2. Severe "critical" SLE flare defined as:

3. BILAG 2004 A flare in CNS system

4. or any SLE manifestation requiring more immunosuppression than allowed within theprotocol in the physician's opinion

5. Pregnant or lactating. Woman who have child bearing potential must have two negativepregnancy test results with a sensitivity of ≥ 25 mIU/mL: one from a serum pregnancytest at day -8 to day -10 of screening and another from a urine pregnancy test at day 1 prior to randomisation. If the timeline is shortened because of clinical urgency,then there must be a negative serum pregnancy test with a sensitivity of ≥ 25 mIU/mLwithin 1-2 days before study start

6. Patients not willing for their GP to be informed of their participation in this study

7. Patients should not be on or require maintenance steroids and should not have had morethan 12 weeks of steroids in the period immediately preceding recruitment irrespectiveof dose

8. Patients that had received more than 2.0g of IV methyl prednisolone in the previous 4weeks

9. Prior use within 12 months of screening visit of therapeutic monoclonal antibody, or Bor T cell modulating 'biologic' use

10. Prior use within 6 months of the screening visit of Intravenous immunoglobulin /plasma exchange OR Cyclophosphamide

11. Active infections, including but not limited to the human immunodeficiency virus (HIV), and hepatitis B (including prior infection as judged by positive Hepatitis Bcore antibody) or Hepatitis C or tuberculosis

12. Receipt of a live-attenuated vaccine within 3 months of study enrolment

13. In the investigator's opinion, patients that are at high risk for infection (includingbut not limited to indwelling catheter, dysphagia with aspiration, decubitus ulcer,history of prior aspiration pneumonia or recurrent severe urinary tract infection)

14. Prior history of invasive fungal infections

15. History of any cancer

16. In female patients, known history of cervical dysplasia CIN Grade III cervical highrisk human papillomavirus or abnormal cervical cytology other than abnormal squamouscells of undetermined significance (ASCUS) within the past 3 years. The patient willbe eligible after the condition has resolved (e.g., follow-up HPV test is negative orcervical abnormality has been effectively treated >1 year ago)

17. Any concomitant medical condition or abnormal blood results that in the investigator'sopinion, or after discussion with the CI, places the participant at risk byparticipating in this study.

18. Comorbidities requiring systemic corticosteroid therapy.

19. Current substance abuse.