SaO041
PROSPECTIVE LONG TERM FOLLOW UP OF THE RITUXILUP STEROID SPARING REGIMEN IN LUPUS NEPHRITIS

Introduction and Aims: Lupus nephritis (LN) is a relapsing/remitting condition & much of the long-term damage relates to oral steroid use. In a single centre prospective cohort study, the Rituxilup regimen (2 doses Methylprednisolone 500mg & Rituximab 1g, 2 weeks apart, followed by maintenance Mycophenolate Mofetil alone) was a safe, effective treatment for ISN/RPS class II/IV/V lupus nephritis (Ann Rheum Dis 2013) over 1 year follow-up. We now report outcomes over ≥ 5 years.

Methods: By May 2014 of the initial cohort of 50 patients; 4 lost to follow-up & 4 had < 5 years follow-up. We report outcomes for the remaining 42. Definitions: Complete Remission (CR):urine PCR<50mg protein/mmol creatinine + creatinine no > than 15% above baseline; Partial Remission (PR):uPCR <300mg/mmol + >50% fall from baseline + creatinine no > than 15% above baseline. Renal flare: uPCR>100mg/mmol on 2 consecutive visits + >50% above remission value +/ or creatinine rise >30% above baseline OR biopsy proven relapse. Non-Response (NR):failure to achieve CR or PR.

Results: 42 patients followed for median of 77 months (24-96). CR/PR achieved in 37 (88%) & median time to remission 9 months (1-36). There were 5 (12%) NR. Importantly in the 39 where data available, 77% (30) never required oral steroids, 10% (4) had < than 4 weeks, & just 13% (5) required long term use, usually after flare. 4 (9%) patients died (median age 72yrs (61-76)). Those who died were much older at presentation (median age 67 yrs (59-73)) vs survivors (39 yrs (18-74)). 5 (12%) needed renal replacement therapy at a median time of 60 months (36-90), 2 of whom later died. Of the 37 patients who achieved CR/PR, 18 (48%) had no renal flare. Median time to renal flare in the rest (52%) was 24 months (9-64). Baseline LN class significantly influenced rate of & time to flare: Class III 0/5; Class V 6/16 (37%) & Class IV 13/16 (81%; p=0.002 vs class III or V). Flares were associated with non-adherence (2), MMF intolerance (2), pregnancy (5, all on azathioprine, 2 during pregnancy), development of ANCA associated vasculitis (1), CMV colitis (1). Repeat biopsy: if class V at baseline, all class V at flare; if class IV at baseline, at flare, 6 class IV, 1 AASV, 4 class V, & 2 class III. Most (79%) flares were treated without oral steroids & majority re-dosed with rituximab (13/19). NR &/or creatinine >120umol/l at baseline predicted poor outcomes whereas flares did not. Median creatinine umol/l(range) at baseline & latest f/up respectively: no flare 89(54-268) & 75(57-199); flare 113(56-383) & 70 (57-314)+2 in ESRF; NR 96 (71-125) & 131(86-169)+2 ESRF.

Conclusions: The Rituxilup regimen led to remission, preservation of renal function & minimal oral steroid use in the majority of patients over a prolonged period. Flares were not uncommon, mostly responded to retreatment with no oral steroids & did not predict poor outcomes. Baseline creatinine >120mmol/l or failure to achieve PR at 6 mths predicted poor outcomes. The minimal use of oral steroids should reduce long-term side effects especially CV risk. The Rituxilup trial (NCT01773616) starting Q1 2015 will address efficacy & safety in an international multicentre randomised controlled trial.