Kidney Week

Abstract: TH-PO1162

RITUXILUP: An Open-Label Randomised Multicentre Controlled Trial of Rituximab and Mycophenolate Mofetil (MMF) Without Oral Steroids for the Treatment of Lupus Nephritis

Session Information

• Late-Breaking Clinical Trials Posters
  October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• No subcategory defined

Authors

• Lightstone, Liz, Imperial College London, London, United Kingdom

Liz Lightstone,

• Wilson, Hannah R., Imperial College London, London, United Kingdom

Hannah R. Wilson,

• Szigeti, Matyas, Imperial College London, London, United Kingdom

Matyas Szigeti,

• Babalis, Daphne, Imperial College London, London, United Kingdom

Daphne Babalis,

• Cook, H. Terence, Imperial College London, London, United Kingdom

H. Terence Cook,

• Bruce, Ian N., University of Manchester, Manchester, United Kingdom

Ian N. Bruce,

• Cairns, Tom, Imperial College Healthcare NHS Trust, London, United Kingdom

Tom Cairns,

• D'Cruz, David, Guy's and St. Thomas' Hospitals NHS Foundation Trust, London, United Kingdom

David D'Cruz,

• Emery, Paul, University of Leeds, Leeds, United Kingdom

Paul Emery,

• Griffith, Megan, Imperial College Healthcare NHS Trust, London, United Kingdom

Megan Griffith,

• Hewins, Peter, University Hospital Birmingham, West Midlands, United Kingdom

Peter Hewins,

• Hull, Richard, King's College Hospital NHS Foundation Trust, London, United Kingdom

Richard Hull,

• Isenberg, David, University College London, London, United Kingdom

David Isenberg,

• Jayne, David R.W., University of Cambridge, Cambridge, United Kingdom

David R.W. Jayne,

• Levy, Jeremy B., Imperial College Healthcare NHS Trust, London, United Kingdom

Jeremy B. Levy,

• Marks, Stephen D., Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom

Stephen D. Marks,

• Mason, Philip David, Oxford Kidney Unit, Oxford, United Kingdom

Philip David Mason,

• Salama, Alan D., University College London, London, United Kingdom

Alan D. Salama,

• Topham, Peter S, University Hospitals of Leicester NHS Trust, Leicester, United Kingdom

Peter S Topham,

• Wessels, Diane Julie, Royal Stoke University Hospital, Stoke, United Kingdom

Diane Julie Wessels,

Group or Team Name

• on behalf of the RITUXILUP Trial Study Group

Background

A key challenge in lupus nephritis (LN) is to treat effectively whilst minimising treatment related toxicity. The investigator led RITUXILUP trial hypothesised that rituximab (RTX), methyl prednisolone (MP) & mycophenolate mofetil (MMF) but without oral steroids (OS) would be non-inferior to standard of care (MP, MMF & OS) in inducing complete remission (CR) at 1yr.

Methods

The trial primary objective was CR at 1yr defined by urine protein/creatinine ratio (uPCR) of ≤50mg/mmol, eGFR (CKD-Epi) ≥60mls/min, or without a fall of >20% if baseline <60mls/min, & without extra steroids above a strictly defined limit. Inclusion criteria: age 12-75yrs, renal biopsy within 8 weeks (ISN/RPS Class III or IV, (A or A/C) or class V), uPCR ≥100mg/mmol & not on maintenance OS. Patients randomised 1:1 all received MP 500mg d1+d15 & MMF with (SoC arm) tapering OS (from 0.5mg/kg) or (RTX arm) RTX 1g d1+d15 & no OS

Results

We needed to recruit minimum 210 patients for 80% power. However, over 2 yrs only 25 (13 RTX, 12 SoC; Female 88%; Non white 68%) were enrolled as the majority of otherwise eligible patients were on longterm OS. The trial terminated early due to slow recruitment & withdrawal of funding. Median (IQR) days follow up (f/up) for primary endpoint: RTX arm 336(253,356); SoC arm 354.5(306,365).
Key results n (%):
CR at 1 yr or latest f/up if <1yr: RTX 6 (46) vs SoC 4 (33) (1 randomised to SoC, withdrew & received RTX)
CR (+steroid deviation): RTX 2 (15) vs SoC 1 (8)
PR: RTX 3 (23) vs SoC 6 (50)
Non response: RTX 2 (15) vs SoC 1 (8)
Significant difference in median total OS exposure over trial : 0mg in RTX vs 3570mg in SoC & equivalent daily dose including the MP 3.6mg/day in RTX vs 13.7mg in SoC
SAEs: RTX 4 in 3 pts & SoC 2

Conclusion

Doing trials in LN remains challenging. Whilst limited, RITUXILUP provides the first RCT data ever to support our hypothesis that LN can be effectively treated without oral steroids. The RTX arm CR is superior to that in most trials despite minimal steroids. A pragmatic future trial will include patients on longterm low dose OS with no dose increase in RTX arm

Funding

• Commercial Support – F.Hoffman-La Roche Ltd