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

Inclusion Criteria:

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

2. Active lupus nephritis, as defined by kidney biopsy within the prior 6 weeks assessed by the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification:

   1. class III (A or A/C) with active lesions in at least 20% of the viable glomeruli, or
   2. class IV-S (A or A/C), or
   3. class IV-G (A or A/C) and / or
   4. class V and
   5. urine protein-to-creatinine ratio >100 at visit -1 or at any time within 14 days before visit -1.
3. No contraindications to the use of IV methyl prednisolone, MMF, oral steroids or rituximab
4. Ability to provide informed consent.
5. Willing to use appropriate contraception

Exclusion Criteria:

1. Aged <12 years or >75 years

2. Inactive lupus nephritis, as defined by kidney biopsy within the prior 6 weeks assessed by the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification:

   1. class III (A or A/C) with active lesions in fewer than 20% of the viable glomeruli , or
   2. class III C or
   3. class IV-S (C), or
   4. class IV-G (C)
3. Obsolescence of >50% of the glomeruli or tubulointerstitial scarring of >50%
4. Unable or unwilling to give informed consent

5. Severe "critical" SLE flare defined as:

   1. BILAG 2004 A flare in CNS system
   2. Total of more than 3 BILAG 2004 As simultaneously
   3. or any SLE manifestation requiring high dose steroids in the physician's opinion
6. Pregnancy
7. Breast feeding
8. At risk of pregnancy and unwillingness to use a medically acceptable form of birth control (including but not limited to a diaphragm, an intrauterine device, progesterone implants or injections, oral contraceptives, the double-barrier method, or a condom).
9. Patients should not be on or require maintenance steroids and should not have had more than 4 weeks of steroids in the period immediately preceding recruitment irrespective of dose.
10. Therapeutic monoclonal antibody, or B or T cell modulating 'biologic' use within 12 months of visit -1.
11. Intravenous immunoglobulin / plasma exchange or pulsed intravenous steroid within 12 months of visit -1
12. Use of cyclophosphamide within the previous 12 months
13. Use of other experimental therapeutic agents within the past 60 days.
14. eGFR <30mls/min/1.73m2
15. Serious infection with the previous 3 months requiring hospitalization or IV antibiotic therapy
16. Active infections, including but not limited to the human immunodeficiency virus (HIV), and hepatitis B or C and tuberculosis. Exclude latent TB unless proof of adequate treatment
17. Receipt of a live-attenuated vaccine within 3 months of study enrollment.
18. In the investigator's opinion, patients that are at high risk for infection (including but not limited to indwelling catheter, dysphagia with aspiration, decubitus ulcer, history of prior aspiration pneumonia or recurrent severe urinary tract infection)
19. Prior history of invasive fungal infections
20. History of cancer, except carcinoma in situ and treated basal and squamous cell carcinomas.
21. Known history of cervical dysplasia CIN Grade III cervical high risk human papillomavirus (HPV) positivity or abnormal cervical cytology other than abnormal squamous cells of undetermined significance (ASCUS) within the past 3 years. The patient will be eligible after the condition has resolved (eg, follow-up HPV test is negative or cervical abnormality has been effectively treated >1 year ago
22. Severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, pulmonary, cardiac, or neurological disease (or, in the investigator's opinion, any other concomitant medical condition that places the participant at risk by participating in this study) with the exception of diseases or conditions related to active SLE.
23. Comorbidities requiring corticosteroid therapy.
24. Current substance abuse.