Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Early Treatment with Rituximab (RTX) in Newly Diagnosed Systemic Lupus Erythematosus (SLE) Patients: A Steroid Sparing Regimen.
Ezeonyeji2, Amara N., Isenberg1, David A.
The efficacy of a RTX as induction therapy enabling long-term steroid therapy reduction or withdrawal has recently been reported in patients with lupus nephritis by Pepper et al.1 We describe a RTX/Azathiaprine (AZA) based steroid sparing regimen given in 9 newly diagnosed mostly non-renal patients with SLE.
Patients and Methods:
Nine female patients fulfilling at least 4 of the revised ACR criteria for the diagnosis of SLE were treated. Mean age at time of B cell depletion therapy was 39 years, Mean duration of symptoms prior to treatment was 16.5 months (range 496). Eight were treated with two intra-venous (iv) infusions of RTX (1000mg) and methylprednsiolone (2 × 100mg) and one iv 750mg infusion of cyclophosphamide (CYC). One patient received 375mg/m2 equivalence RTX over 3 weeks with CYC. Post treatment all patients received AZA and any steroid treatment rapidly weaned [table 1]. The British Isles Lupus Assessment Group (BILAG) disease activity index was used for both individual organ system assessment and as a global index. The patients full blood count, serum creatinine (Cr), serum C3, immunoglobulin G (IgG), erythrocyte sedimentation rate (ESR), anti-dsDNA and circulating B lymphocytes (CD19+) count were tested at baseline, 1, 3, 6 and 12 months post treatment.
Table 1. Patient characteristics: prednisolone; pred, weeks; wks
|Patient||Disease manifestation at baseline||Therapy pre-RTX||Therapy post-RTX|
|1||Headache, rash, pleurisy, proteinuria||Pred 30 mg ¯ over 8 weeks for flare||Pred 40 mg ¯ over 4 wks|
|2||Rash, lymphadenopathy, angioedema, fevers, [uarr] anti-dsDNA, lymphopenia, ¯ C3||Depomedrone 120mg i.m.||Pred 20mg ¯ over 8 wks at 2 months for flare|
|3||Rash, headache, alopecia, aicca symptoms, ¯ C3, lymphopenia,||None||None|
|4*||Rash, headache, thrombocytopenia, anaemia, proteinuria [uarr] anti-dsDNA, lymphopenia, ¯ C3||AZA (stopped) & Pred 2.5 mg Pred 30mg ¯ over 2 wks for thrombocytopenia||Pred 60mg ¯ over 8 wks|
|5||Rash, livido reticularis, serositis, oral ulcers, proteinuria, [uarr] anti-dsDNA, lymphopenia, ¯ C3.||Pred 40mg stat||Pred 40mg ¯ over 12 wks AZA|
|6||Polyarthritis, [uarr] anti-dsDNA, lymphopenia, ¯ C3||Pred 7.5mg for 2 wks||AZA|
|7||Skin rash, raynauds, alopecia, pleurisy, [uarr] anti-dsDNA, lymphopenia.||Pred 7.5mg for 12 wks||AZA|
|8||Rash, alopecia, raynands, arthralgia, ¯ C3||None||AZA|
|9||Polyarthritis, [uarr] anti-dsDNA, lymphopenia||AZA for colitis||AZA|
All patients achieved B cell depletion (CD 19 < 0.005 ×109/l. at 1 month). Patient 3 re-populated at 6 months but did not flare. The mean BILAG global score fell from 12.1 (SD 8.6) (n=9) at baseline to 7.4 (SD 4.7) (n=7) at 1 month, 3.9 (SD 2.3) (n=7) at 3 months, 3.5(SD 1.3) (n=4) at 6 months, and 1.5 (SD 0.7) (n=2) at 1 year. Patients 7 achieved improvement of BILAG grades A®D for mucocutaneous manifestations by 3 months and patient 2 and 8 by one year although patient 2 had a musculoskeletal flare at 2 months requiring steroid treatment. No patient developed any major sustained deterioration i.e. new A or D®B scores. Manifestations such as rash, arthritis, fever, thrombocytopenia and pleurisy responded well. Mean ESR fell from 76 to 32.9 at 1 month (n=9). Anti-dsDNA antibody levels fell by >50% in 3 patients. Serum C3 level did not change significantly except for patient 7 where it rose from 0.4 to 1.04 (NR 0.8 to 1.8g/l) by 3 months. Cr was stable throughout. In patient 1 and 5, urine protein: creatinine ratio (PCR) was stable at 6 and 3 months respectively although patient 5 required a renal biopsy as the PCR was 236 mg/mmol at 3 months. PCR fell from 104 to 15 mg/mmol by 1 month in patient 4. Mean total serum IgG fell modestly from 20.3 to 13.8 g/l.
Treatment was safe and well tolerated. There were no adverse events on follow up.
A RTX/AZA protocol as a steroid sparing regimen is safe and effective in newly diagnosed patients with SLE.
To cite this abstract, please use the following information:
Ezeonyeji, Amara N., Isenberg, David A.; Early Treatment with Rituximab (RTX) in Newly Diagnosed Systemic Lupus Erythematosus (SLE) Patients: A Steroid Sparing Regimen. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1153