Rituximab May Not Halt Progression to ESRD

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Shirish Sangle, MD
Shirish Sangle, MD

Effective at treating SLE but does not halt progression in some patients.

 

BOSTON—Rituximab is highly effective for treating resistant systemic lupus erythematosus (SLE), but, in certain patients, the medication does not prevent progression to end-stage renal disease (ESRD), British researchers conclude.

 

These patients include those with rapidly progressive crescentic lupus nephritis and renal impairment.

 

“Rituximab, for a period of time, has shown excellent results in the treatment of difficult lupus. However, in a small group of patients, it doesn't seem to help,” said lead investigator Shirish Sangle, MD, a clinical fellow at St. Thomas' Hos-pital in London.

 

He and his colleagues studied 16 patients (14 women) with severe, active SLE receiving rituximab on an open-label basis. All patients had disease refractory to conventional immunosuppressive therapy and all met the revised ACR classification criteria for SLE. Twelve patients had biopsy proven lupus nephritis (WHO Class III, IV, and V), two patients had SLE complicated by immune thrombocytopenia (one with splenectomy), one patient had extensive cutaneous disease, and one had arthritis and resistant serositis (pericarditis and pleuritis). Of the 16 patients, 10 were Caucasian, five were Afro-Caribbean and one was Asian. Patients ranged in age from 23 to 58 (mean age 36 years).

 

Patients received two rituximab 100 mg infusions two weeks apart along with IV cyclophosphamide 500 mg and methylprednisolone 500 mg. Other immunosuppressive agents except for steroids were stopped. The investigators measured clinical response before and after treatment using the British Isles Lupus Assessment Group (BILAG) score. The extent and duration of B lymphocyte depletion was documented.

 

After four to six months, nine patients improved clinically, with mean BILAG global scores dropping from 16 to 5, Dr. Sangle reported at the American College of Rheumatology annual meeting. At six months, however, one patient flared despite depleted B lymphocytes and seven patients failed to show any significant or sustained clinical improvement despite a mean B lymphocyte count of 0.004 x 109/L.

 

The mean BILAG global scores were 28 pre-treatment and 23 post-treatment. One patient with cutaneous lupus showed transient improvement but then relapsed at four months. Remission in the patient with arthritis and serositis lasted only for four months. 

 

Five patients with severe proliferative, crescentic lupus nephritis (mean activity score 12/24, mean crescents 38%) with elevated serum creatinine (mean creatinine 278 µmol/L) all failed to respond to rituximab and progressed rapidly to ESRD and dialysis. Four patients deteriorated de-spite complete and prolonged B lymphocyte depletion at six months. 

 

Co-investigator Rachel Davies, MD, a senior lecturer at St. Thomas' Hospital, said rituximab appeared not to work when it was given to patients with severe disease and impaired renal function. It could be that these patients are being treated too late in the progression of their disease, she said.

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