Session Information
Title: Systemic Lupus Erythematosus - Clinical Aspects I - Renal, Malignancy, Cardiovascular Disease
Session Type: Abstract Submissions (ACR)
Background/Purpose: B-cell depletion therapy by rituximab has been reported to be useful for treatment of lupus nephritis (LN) in many observational uncontrolled studies, however, placebo-controlled phase III study, LUNAR has failed to find clinical benefit of rituximab over placebo1). The interpretation of the study is controversial because of intense background MMF. Then, rituximab is still gaining attention as a treatment option for LN and recent ACR guideline recommends rituximab as an alternative treatment option for refractory LN with class III/IV2). In order to examine efficacy and safety of rituximab in LN who responded inadequately to conventional therapy, a post-hoc analysis was done for subset of LN patients who entered into Japanese phase II clinical study in refractory SLE.
Methods: Patients (pts) with proteinuria, Upr/Ucr >1.0 and active urine sediment were eligible to the study. The treatment protocol was the same as EXPLORER and LUNAR and rituximab was administrated at a dose of 1,000mg/body on days 1, 15, 169 and 183. After the first dose of rituximab, background steroid was tapered by 20% every two weeks. Pts were followed for 53 weeks and renal response was examined by the criteria used in LUNAR1) and ACR3).
Results: A total of 34 pts were enrolled into the study and 17 pts had renal involvement with Upr/Ucr >1.0 (median:2.2, range:1.0-10.0). 10 out of 17 pts were biopsy-verified class III/IV, and 9 pts had a treatment history with steroid pulse and/or IVCY. Median predonisolone dose before rituximab therapy was 50 mg/day (range:15-100 mg/day). In all 17 pts, peripheral blood of B-cells depleted after the first rituximab and kept low throughout the study. 2 pts discontinued the study prematurely because of renal flare and were classified as non-responder. Overall response rate by ACR criteria were 58.8%; complete renal response (CR) 35.3%, partial renal response (PR) 23.5%, 95%CI:32.9-81.6%. Response rate with LUNAR were 52.9% (CR 29.4%, PR 23.5%, 95%CI:27.8-77.0%). As far as the response was evaluated in 10 pts with histologically confirmed class III/IV, overall response rate by ACR or LUNAR were 70.0% (CR 40.0%, PR 30.0%, 95%CI:34.8-93.3%) and 60.0% (CR 40.0%, PR 20.0%, 95%CI:26.2-87.8%), respectively. Successful steroid tapering achieved in all 15 pts who completed the study and median predonisolone dose at Week 53 was 5 mg/day (4-12 mg/day). As for the safety, rituximab was well tolerated and 6 infusion-associated reactions were observed in 3 pts, which were all grade 1-2 in severity. Three grade 3/4 adverse events were observed in 2 pts for which causal relationship with rituximab was not completely excluded: herpes simplex (G3), neuralgia (G3) and leukocytopenia (G4).
Conclusion: 1. Rituximab is effective for treatment of LN who were poorly controlled by conventional therapy and recent ACR guideline for LN is also applicable to Japanese patient. 2. Further studies will be needed to clarify and maximize the benefit of rituximab for treatment of LN. 3. International cooperative study such as RING (Rituximab for Lupus Nephritis in Remission as a Goal) is expected to provide new insight in rituximab in LN.
Ref: 1)Arthritis Rheum 2012;64:1215-1226. 2)Arthritis Care Res 2012;64:797-808. 3)Arthritis Rheum 2006;54:421-432.
Disclosure:
Y. Tanaka,
None;
K. Yamamoto,
None;
T. Takeuchi,
None;
N. Miyasaka,
None;
T. Sumida,
None;
T. Mimori,
None;
T. Koike,
None;
K. Endo,
Zenyaku Kogyo Co., Ltd.,
3.
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