Background/Purpose:

Systemic lupus erythematosus (SLE) is often complicated by resistance or partial response to initial immunosuppressive regimen and flares after initial response.  Optimal management of these patients is unclear due to lack of scientific evidence.   There is limited data suggesting that the combination of cyclophosphamide (CYC) and rituximab (RTX) may have efficacy in recurrent and treatment resistant lupus. We present our experience with intravenous (IV) CYC plus RTX combination and its comparison to CYC only therapy.

Methods:

Data   from SLE patients who were treated with IV CYC monotherapy only or IV CYC and RTX combination from 2000-2013 was retrospectively reviewed.  Patient’s demographic information, SLE duration, SLE manifestations, co-morbidities, relevant labs, response to therapy and post-treatment infections were recorded every month for the first 6 post –treatment months and then every 3 months up to 60 months( if available) or until last data entry.  Patients with incomplete data or insufficient follow-up(less than 6 months post-treatment) were not included.  IV CYC monotherapy was given according to the  NIH standard protocol for the treatment of lupus nephritis.  IV CYC and RTX combination therapy regimen consisted of simultaneous administration of IV CYC and 2 doses of RTX 1000 mg given 15 days apart. Combination regimen was prescribed based on clinician’s discretion most commonly for recalcitrant  or recurrent flares of lupus nephritis(LN). Predetermined definitions (based on published literature) were used to record flares (renal vs. non-renal) and response (complete, partial or no response). Statistical analysis was done using SAS software (SAS Inc., Cary, NC). 

Results:

A total of 43 SLE pts. with adequate follow up were identified: 31 (72%) received CYC; 12 (28%) received CYC plus RTX. Indications for   combination treatment were partial response or recurrent LN (10/12), CNS lupus(1/12) and treatment resistant extra-renal SLE(1/12). Most (75%) patients treated with CYC and RTX combo were previously treated with IV CYC , most commonly for  lupus nephritis. There was no difference in overall survival between CYC only and CYC and RTX combo groups.  In patients receiving combo treatment, median duration of follow –up was 36 months (6-50 months) prior to combo treatment and 21 months (6-60 months) after receiving the combo treatment.   In the 12 patients who received CYC plus RTX,  number of flares before receiving CYC and RTX combo was significantly higher= 38(Renal flares=26; non-renal flares=12) as compared to after receiving combo=13(Renal=3; non-renal=10).  There was no significant increase in bacterial, viral or fungal infections after receiving combo therapy.

 Conclusion:

CYC and RTX combination regimen may have efficacy  in reducing renal and non-renal lupus flares .  This does not appear to be  associated with increased risk of infections.  Long term sequelae if any, of this regimen is not  known.  Our study has inherent limitations due to its retrospective nature  and small sample size.  Based on these preliminary results we are planning a clinical trial  studying the efficacy and tolerability of CYC/RTX combination  in patients with recurrent severe SLE.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/cyclophosphamide-and-rituximab-combination-treatment-for-severe-systemic-lupus-erythematosus-is-effective-and-well-tolerated/