PARIS – Treatment with rituximab in patients with refractory lupus nephritis was associated with significant long-term improvement in symptoms, histology, and laboratory markers in a prospective study.
Over a median follow-up period of 18 months (interquartile range, 12-36 months), the drug normalized proteinuria and was associated with a median reduction in glucocorticoid use of 28 mg/day, according to Dr. Maria Tsanyan of the Nasonova Research Institute of Rheumatology, Moscow.
She and her colleagues followed 60 patients with refractory lupus nephritis who had a median age of 26 years and median disease duration of 37.5 months. At baseline, the patients’ median glomerular filtration rate was 46 mL/min, and their median amount of proteinuria was 1.83 g/day. A total of 14 patients (23%) had nephrotic syndrome.
All patients had failed prior therapy. These treatments included high-dose glucocorticoids (45%), pulsed high-dose glucocorticoid and cyclophosphamide (90%), mycophenolate mofetil (17%), azathioprine (7%), hydroxychloroquine (17%), and cyclosporine A (8%).
Treatment with rituximab varied according to clinical status and response. The initial doses were 1,000 mg in 25 patients and 2,000 mg in 30 patients. Five patients did not receive a full initial course of rituximab because of the development of end-stage renal disease, including four who received only 500 mg and one who received 1,500 mg.
Most (37) required more than one course: 21 needed two courses, 11 needed three, 4 needed four courses, and 1 received five courses of the drug.
In response to an audience member’s question about the basis on which the investigators decided to re-treat patients with rituximab, Dr. Tsanyan said that they tried to achieve complete responses in patients with disease exacerbation or partial response at 6 months or 12 months after the initial dose.
Based on the Systemic Lupus Erythematosus International Collaborating Clinics renal activity/response exercise criteria, 58% had a complete response, 22% had a partial response, 12% were nonresponders, and 8% died of acute renal failure. Overall, 28% of patients had an exacerbation of disease during treatment.
There was no difference in response between patients who received 1,000 mg and 2,000 mg rituximab, she said at the annual European Congress of Rheumatology.
By 6 months of treatment, the median Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score had decreased from 20 to 4. This improvement held at 12 months. By 42 months, the median score had dropped to 2. By SLEDAI-2K index, 50% were considered to be complete responders, 30% partial responders, and 12% nonresponders.
Antibodies to double-stranded DNA fell from a mean of 67.7 U/mL at baseline to 34.5 U/mL at 42 months. Daily glucocorticoid use dropped from 35 mg to 7.5 mg.
C3 and C4 complement components also improved. C3 rose from 0.7 to 0.98 g/L, and C4 from 0.1 g/L to 0.24 g/L. Daily proteinuria fell from 1.6 g/day to 0.01 g/day and serum total protein rose from 59 g/L to 72 g/L.
Sixteen patients had renal biopsies both at baseline and at the end of their follow-up period. Of 14 patients who had World Health Organization class IV nephritis at baseline, 5 were unchanged, 3 moved to class III, 5 to class II, and 1 to class I. Two class III patients improved to class I.
There were 13 adverse events, all of which occurred during the first 3 months of rituximab therapy. These included pneumonia (4), aspergillosis (1), bronchitis (1), cystitis (2), shingles (3), furunculosis (1) and pityriasis versicolor (1).
Dr. Tsanyan did not have any financial disclosures.