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.

UCL Div of Medicine, Room 331, 3rd Floor, London, United Kingdom
University College London Hospital NHS Trust, London, United Kingdom

Introduction:

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 4–96). 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

PatientDisease manifestation at baselineTherapy pre-RTXTherapy post-RTX
1Headache, rash, pleurisy, proteinuriaPred 30 mg ¯ over 8 weeks for flarePred 40 mg ¯ over 4 wks
2Rash, lymphadenopathy, angioedema, fevers, [uarr] anti-dsDNA, lymphopenia, ¯ C3Depomedrone 120mg i.m.Pred 20mg ¯ over 8 wks at 2 months for flare
3Rash, headache, alopecia, aicca symptoms, ¯ C3, lymphopenia,NoneNone
4*Rash, headache, thrombocytopenia, anaemia, proteinuria [uarr] anti-dsDNA, lymphopenia, ¯ C3AZA (stopped) & Pred 2.5 mg Pred 30mg ¯ over 2 wks for thrombocytopeniaPred 60mg ¯ over 8 wks
5Rash, livido reticularis, serositis, oral ulcers, proteinuria, [uarr] anti-dsDNA, lymphopenia, ¯ C3.Pred 40mg statPred 40mg ¯ over 12 wks AZA
6Polyarthritis, [uarr] anti-dsDNA, lymphopenia, ¯ C3Pred 7.5mg for 2 wksAZA
7Skin rash, raynauds, alopecia, pleurisy, [uarr] anti-dsDNA, lymphopenia.Pred 7.5mg for 12 wksAZA
8Rash, alopecia, raynands, arthralgia, ¯ C3NoneAZA
9Polyarthritis, [uarr] anti-dsDNA, lymphopeniaAZA for colitisAZA

Results:

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.

Adverse Events:

Treatment was safe and well tolerated. There were no adverse events on follow up.

Conclusions:

A RTX/AZA protocol as a steroid sparing regimen is safe and effective in newly diagnosed patients with SLE.

References:

(1)Pepper, R, et al Nephrol Dial Transplant. 2009 12:3717–23.

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
DOI: 10.1002/art.28919

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