A dose-escalation study of rituximab for treatment of systemic lupus erythematosus and Evans' syndrome: immunological analysis of B cells, T cells and cytokines

Abstract

In addition to B-cell depletion, modification of B-cell and T-cell phenotypes as well as cytokine profiles may be involved in the action of rituximab.

Efficacy and safety of rituximab therapy for systemic lupus erythematosus: a systematic review and meta-analysis

“…Tables 1 and 2 show a summary of included studies. We found 2 RCTs (Furie et al, 2009;Merrill et al, 2011) and 19 observational studies (Leandro et al, 2002;Leandro et al, 2005;Vigna-Perez et al, 2006;Gunnarsson et al, 2007;Tokunaga et al, 2007;Sutter et al, 2008;Tamimoto et al, 2008;Melander et al, 2009;Pepper et al, 2009;Catapano et al, 2010;Lateef et al, 2010;Ramos-Casals et al, 2010;Terrier et al, 2010;Pinto et al, 2011;Roccatello, 2011;Tony et al, 2011;Turner-Stokes et al, 2011;Vital et al, 2011;Arce-Salinas et al, 2012).…”

“…Dose of rituximab The dosing of rituximab in SLE patients varied between studies; some followed the rheumatoid arthritis guidelines ((0.5-1.0 g)×2 infusions) (Leandro et al, 2002;Vigna-Perez et al, 2006;Pepper et al, 2009;Terrier et al, 2010;Pinto et al, 2011), and some followed a lymphoma schedule (375 mg/m 2 × 4 weeks) (Gunnarsson et al, 2007;Tokunaga et al, 2007;Sutter et al, 2008;Tamimoto et al, 2008;Melander et al, 2009;Catapano et al, 2010;Lateef et al, 2010;Ramos-Casals et al, 2010;Terrier et al, 2010;Roccatello et al, 2011;Vital et al, 2011;Arce-Salinas et al, 2012). In our review, except for the German Registry of Autoimmune Diseases (GRAID) studies in Germany, 268 (50.9%) cases received a rituximab (0.5-1.0 g)×2 infusions, 211 (40.1%) received a rituximab infusion of 375 mg/m 2 × 4 weeks, and 46 (8.7%) cases received a dose of rituximab ≤375 mg/m 2 ×2 weeks.…”

“…The SLEDAI data from studies 4 (Gunnarsson et al, 2007), 6 (Sutter et al, 2008), 7 (Tamimoto et al, 2008), 12 (Roccatello et al, 2011), and 17 (Terrier et al, 2010) were included in the meta-analysis. Although studies 3 (Vigna-Perez et al, 2006), 5 (Tokunaga, 2007, 13 (Arce-Salinas et al, 2012), and 16 (Pinto et al, 2011) also reported on SLEDAI, they were excluded due to missing data.…”

“…The homogeneity test χ 2 value of prednisone dose data from studies 4 (Gunnarsson et al, 2007), 7 (Tamimoto et al, 2008), 13 (Arce-Salinas et al, 2012, 14 (Catapano et al, 2010), 15 (Pepper et al, 2009), 16 (Pinto et al, 2011, and 17 (Terrier et al, 2010) was 179.25 (P=0.00001 (<0.05)) and these studies were therefore, not considered homogeneous. The combined effect was calculated using the random effects model, and was found to be Z=2.73 (P=0.006 (<0.05)), indicating that treatment with rituximab had significant effects on prednisone dose when compared to baseline (Fig.…”

Immunologic Reconstitution After Rituximab in Systemic Lupus Erythematosus: Why Should We Care?

“…The present article adds to rather limited data indicating that effects on the T cell compartment may be key to responses in human SLE after B cell depletion therapy 6,7 . These data include the variable finding of increased regulatory T cells after B cell depletion 7 , decreased T cell activation 6 , and a shift in the Th1/Th2 balance 8 . Of note, in contrast to the study by Sfikakis, et al 6 the decreased T cell activation observed in the present study was not confounded by high-dose steroids.…”