Objectives The aim of this study was to evaluate the long-term clinical, serological and histopathological effects of the therapy with Rituximab (RTM) in patients with lupus nephritis (LN) refractory to conventional treatment. We aimed to investigate the role of second renal biopsy in evaluation of treatment response during the long-term follow up.

Methods 60 patients with LN, followed for a mean time of 18[12-36]months, were included. The median of age of the patients was 26[21-34]y, duration of the diseases was 37,5[16-77]y. Nephrotic syndrome was observed in 14 patients. 23 patients showed a decrease of glomerular filtration rate below 70ml$\ $min. Disease activity was evaluated with the SLEDAI2K (20[14-24] before the treatment). Renal biopsies were performed for histological evaluation at baseline (n=45) and follow-up (n=16).

Results During the long-term follow-up the complete response (CR) rate was 50%, partial response (PR) rate was 30% and 20% of patients did not respond to therapy (8% of them were died as a result of progression of renal failure). The exacerbation was occurred in 28% of patients with LN at 12[12-24] months of follow-up. The exacerbation were treated with repeated courses of RTM. 75% of patients had depleted peripheral B-cells.

There was statistically significant decrease of 24-h proteinuria from baseline (1,6[0,7-2,9]g/day) to 42 months of follow-up (0,01[0-0,9]g/day) (p<0,001). Normalization of 24-h proteinuria was observed in most patients at the 6month of follow-up, which was associated with increased level of serum albumin, followed by normalization of blood pressure at the 3-month of follow-up. This was associated with decreased SLEDAI2K (p<0,004), anti-dsDNA (p<0,002), hematuria (p<0,01), normalization of C3 and C4 components of complement (p<0,01) and decreased daily dose of glucocorticoids (p<0,02) during the long-term follow-up.

According to the results of repeated renal biopsy after therapy with RTM transformation of morphological class of LN in a more “favorable” option was observed in 11 patients, which was accompanied by a CR in most cases. In 5 patients with class IV LN the transition into the class II LN was observed, in 3 patients - from IV to III class, in 1 patient-from IV to I class, in 2 patients-from III to 1 class. In 5 patients with class IV LN morphological class did not change during therapy with RTM. Histological improvement was obvious nearly in all patients with a significant reduction of activity index from 8,0[5,0-9,0] to 3,5[1,0-6,5] (p=0,006). Statistically significant changes in chronicity index was not obtained (p=0,14).

Conclusions Therapy with RTM induced clinical, serological and histological improvements in the majority of patients with refractory LN. The repeated biopsy might provide additional information on long-term renal outcomes and therapeutic response.

Disclosure of Interest None declared

DOI 10.1136/annrheumdis-2014-eular.5679