Objective Severe flare of systemic lupus erythematosus (SLE) often requires aggressive immunosuppressive treatment. The success of the induction treatment is crucial in preventing organ damage. Our aim was to compare the efficacy and safety of iv. cyclophosphamide (CYC) and rituximab (RTX) induction therapy.

Methods In a single center, retrospective setting, the clinical data of patients treated for severe SLE were analyzed. Disease activity and the distribution of organ manifestations were characterized based on the SLEDAI-2K index. Changes in the SLEDAI-2K index and serological markers (anti-dsDNA, complement-3 and -4), the steroid dose - induction (initial iv. methylprednisolone dose), or cumulative - and the proportion of patients achieving low disease activity or remission (clinical SLEDAI = 0, prednisolone ≤5 mg/day) were evaluated at 6 and 12 months. The safety of the treatment was assessed by the number of adverse events and infections.

Results CYC: 33 cases (mean age 42.76±16.72 years). RTX: 35 cases (mean age 40.03±15.67 years). There were no significant differences in initial SLEDAI values (CYC: 17.46±9.47; RTX: 13.11±7.34; p=0.06) and the levels of the serological markers. With both treatments, SLEDAI and serological activity were significantly reduced by months 6 (SLEDAI: CYC: 6.54±4.85; RTX: 4.90±3.79) and 12 (SLEDAI: CYC: 4.92±4.13; RTX: 4.04±4.15), with no significant difference between the two therapeutic agents. However, after 12 months, in the RTX group more patients met remission criteria (CYC: 5.59%; RTX: 19.12%; p=0.017), and both induction (CYC: 1728 mg; RTX: 970.5 mg; p<0.001) and cumulative (CYC: 3970 mg; RTX: 2142 mg; p<0.001) corticosteroid doses were significantly lower. In the CYC group, adverse events occurred more frequently, although not significantly (CYC: 10.29%; RTX: 4.41%; p=0.141). Regarding infections a similar trend was observed (CYC: 20.59%; RTX: 13.24%; p=0.145).

Conclusions In consonance with the EULAR therapeutic recommendations, our results showed that in the setting of a severe SLE flare, CYC and RTX are both highly effective remission-inducing agents. However, a higher rate of clinical remission was achieved with rituximab than with CYC by 12 months. Furthermore, rituximab required significantly lower steroid doses than CYC to achieve these outcomes.