Abstract
OBJECTIVE: Renal involvement is a common extra-glandular lesion in primary Sjögren syndrome (pSS), generally associated with poor prognosis. Early immunotherapy might alleviate renal injury and improve long-term renal function. Growing evidence suggests that rituximab (RTX) is effective for systemic manifestations in pSS. In this retrospective study, we preliminarily investigated the efficacy of RTX on renal involvement in pSS. METHODS: Clinical and laboratory data from the clinical large-scale data application platform of peking University People' s Hospital were collected. From July 2013 to January 2025, 17 patients with secondary renal damage due to pSS who were treated with RTX in the Department of Rheumatology and Immunology and the Department of Nephrology of Peking University People' s Hospital were consecutively included. During the same period, 34 patients treated with conventional immunosuppressive drugs were matched for age, gender, and baseline disease conditions. The RTX group received glucocorticoid therapy along with RTX, while the control group received glucocorticoid therapy along with immunosuppressive drugs for 6 months. We evaluated the effect of different treatments by comparing general laboratory parameters, renal injury index, and immunological features before and after treatment in the two groups. RESULTS: After 6 months, renal function indices showed significant reductions in levels of the urinary N-acetyl-β-glucosaminidase (NAG), beta2-microglobulin (β2-MG), creatinine, and urea nitrogen in the RTX group ( P < 0.01, P < 0.05). It was shown that the levels of 24 h urinary total protein (24h UTP), urinary retinol-binding protein in the RTX group were lower, while the serum potassium in the RTX group were higher than those in the control group, all with no significant difference (P>0.05). Regarding immunological features, the RTX group had significantly lower levels of immunoglobulin G (IgG, P < 0.05) and rheumatoid factor (RF, P < 0.05), and higher levels of complement 3 (C3) and complement 4 (C4) compared with the control group ( P < 0.05). The total European League Against Rheumatism Sjögren syndrome disease activity index (ESSDAI) score and renal score in the RTX group were significantly lower than those in the control group, with statistically significant differences ( P < 0.05). Furthermore, after the 6-month treatment, a higher proportion of patients in the RTX group were able to taper their prednisone dose to lower levels (0-5 mg, quaque die) compared with the control group (64.71% vs. 32.35%, P=0.038). In addition to these positive outcomes, the incidence of infection was 1/17 in the RTX group and 3/34 in the control group. No serious adverse events were observed during the trial. CONCLUSION: Through targeted depletion of pathogenic B cells, RTX had the potential to ameliorate glomerular and tubulointerstitial damage, as well as modulate renal excretion and acid-base equilibrium in pSS patients. It was suggested that RTX might be superior to traditional immunosuppressive drugs, and helpful in glucocorticoid tapering. Meanwhile, medication adherence was guaranteed with a favorable safety profile. Thus, RTX is considered to be a promising option in clinical practice.