Background/Purpose:

Lupus nephritis (LN) is a major cause of morbidity. Many patients with refractory disease can not tolerate conventional immunosuppressive therapy. The aims of this study were to describe the comorbidities at baseline, most relevant manifestations at diagnosis, concomitant medications used with disease-modifying anti-rheumatic drugs and prednisolone in lupus patients given Rituximab (RTX). Additionally, we identified what variables are associated with renal response at 12 months.

Methods:

A 13 year retrospective analysis was completed on 42 LN patients treated with combination therapy of  RTX and cyclophosphamide (CYC). We defined Renal flare (RF), Complete (CR) and Partial (PR) Renal Response according to the EULAR/ERA-EDTA criteria. The response was defined at 12 months after the treatment with RTX.

Results:

Based on 42 patients treated with RTX 2g in combination with CYC 750 mg for active LN: 38 patients were female with a median age at diagnosis of 38 years, interquartile range [IQR: 25 – 46]. 12 (28.6%) were Caucasian, 17 (40.5%) Black, and 10 (23.8%) South-Asian.  The most frequent comorbidities were high blood pressure (52.4%), dyslipidaemia (26.2%), depression (23.8%), skin (26%), pulmonary (26%) and infectious disease (28.6%). 6 (14.3%) had associated autoimmune diseases (APS 7%; Sjögren’s Syndrome 4.8%). The main manifestations at diagnosis were: constitutional in 36 (85.7%), mucocutaneous in 39 (93%), musculoskeletal in 38 (90.5%), hematological in 22 (52.4%), cardiorespiratory in 19 (45.2%), gastrointestinal in 9 (21.4%), neuropsychiatric in 13 (31%) and renal in 38 (90.5%). Prior RTX administration, the most frequently medications used were: MMF in 19 patients (45%), Hydroxychloroquine in 15 (35.7%), Azathioprine in 9 (21.4%) and Prednisone <10mg/d in 25 (60%) and 11-30 mg/d in 13 (31%).

2 patients had class II, 7 class III, 20 class IV, 8 class V, and 4 with mixed (II+III; IV+V; V+III) LN.

At 12 months post-RTX therapy, 14 patients achieved renal response and 15 patients were non responders. 9 patients had a new flare before 12 months, 2 had no retrievable information and 2 patients died at 4 and 5 months post-RTX.

22 out of 42 were retreated due to a flare (Renal/Non renal). Patients with GN type 4 were more prone to flare and required re-treatment with B cell depletion.

The time between first dose of RTX and second treatment was 25 ± 22.4 months.

We found a significant association between renal response at 12 months post-RTX and age (35.64 vs 42.87; p<0.05); lower levels of serum creatinine (91.07 vs 120.38; p<0.05) and higher levels of dsDNA (1063 vs 474; p<0.05) at baseline; absence of dyslipidemia (15.4%; p<0.05) or anaemia (15.4%; p<0.05); absence of cardio-respiratory (23.1%; p<0.05)  and ocular involvement (0%; p<0.05) at diagnosis. We determined that there was no difference with ethnicity, gender, concomitant treatments, type of GN or levels of complement.

Conclusion:

We have shown that patients who achieved a Renal Response at 12 months post-RTX were younger, had a lower levels of creatinine and higher levels of dsDNA at baseline.

More prospective studies and randomized control trials are needed to understand better this complex disease

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-retrospective-observational-study-of-patients-with-lupus-nephritis-treated-with-rituximab-in-combination-with-cyclophosphamide/