Long-term efficacy of anti-CD20 antibodies in refractory lupus nephritis

Abstract

Eight patients with refractory lupus nephritis received rituximab after failing standard sequential therapy and were followed for 104 weeks after the infusion. One patient died secondary to a complicated pregnancy but had stable renal function. Three patients received a re-infusion of rituximab approximately 12 months apart due to a renal flare; during the second year of follow-up, those patients progressed toward ESRD. The four remaining patients demonstrated improvements in SLEDAI score, CrCl, and proteinuria with maintenance of their standard immunosuppressive therapy and did not require a re-infusion of rituximab. Although rituximab as induction therapy for refractory lupus nephritis has been shown to have a good response, its efficacy in long-term assessments demonstrates disappointing results.

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).…”

“…7). , 2012Catapano et al, 2010Gunnarsson et al, 2007Lateef et al, 2010Terrier et al, 2010 Total (95% CI) Heterogeneity: Chi?= 3.70, df = 3 (P = 0.30); I?= 19% Test for overall effect: Z = 7.26 (P < 0.00001) 2012Catapano et al, 2010Gunnarsson et al, 2007Lateef et al, 2010Terrier et al, 2010 Heterogeneity: Chi 2 =3.70, df=3 (P=0.30); I 2 =19% Test for overall effect: Z=7.26 (P<0.00001)…”

“…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 SLEDAI data from studies 4, 6, 7, 12, and 17 was 19.96 (P=0.000 5 (<0.01)) and these studies were therefore, not considered homogeneous.…”

“…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.…”

Люпус-Нефрит: Сучасна Парадигма Лікування

“…Среди препаратов, блокирующих пролиферацию В-клеток, наиболее изученным, безусловно, является ритуксимаб -рекомбинантные химерные (мышь -человек) моноклональные антитела к поверхностным рецепторам В-лимфоцитов -CD20. Предполагаемый механизм действия ритуксимаба, направленный на подавление активности В-клеток, может реализовываться за счет антителозависимой клеточной цитотоксичности, комплементзависимой цитотоксичности, ингибиции клеточной пролиферации и индукции апоптоза В-лимфоцитов Первоначально несколько открытых испытаний и многочисленные сообщения о клинических случаях применения ритуксимаба при ВН вызвали большой оптимизм относительно использования ритуксимаба у пациентов с люпус-нефритом [11,22,29,33]. Однако последующие контролируемые испытания принесли разочарования.…”