ReviewEfficacy of rituximab in 164 patients with biopsy-proven lupus nephritis: Pooled data from European cohorts
Highlights
► Rituximab in lupus nephritis (LN) currently seems to be good in real life, but bad in controlled trials. ► We present 164 patients with biopsy-proven LN treated with rituximab, the majority refractory to standard therapies. ► We found a clinical response in two thirds of patients at both 6 and 12 months (CR=27% at 6 months, 30% at 12 months). ► A different rate of response according to the ISN/RPS histopathological classification was found. ► Patients with mixed proliferative-membranous LN showed a 4-fold rate of CR at 12 months (70%) than type IV LN (22%). ► The main baseline features associated with not achieving CR were nephrotic syndrome and renal failure.
Introduction
Systemic lupus erythematosus (SLE) is considered the most clinically and serologically diverse systemic autoimmune diseases (SAD) because it may affect any organ and display a broad spectrum of clinical manifestations [1], [2]. Renal disease plays a key role in the prognosis of SLE and contributes significantly to the morbidity and mortality of the overwhelmingly-young, female SLE population [3]. Patients with glomerulonephritis have a higher mortality rate in comparison with those without renal involvement, and nearly 10% of patients with lupus nephritis (LN) develop end-stage renal failure requiring dialysis or transplantation [4], [5], [6]. Both nephritis and chronic corticosteroid and immunosuppressive agent use cause significant morbidity and reduced life expectation in SLE patients.
Rituximab is a chimeric antibody against CD20, a surface antigen expressed by B cells. Rituximab was first approved for the treatment of patients with relapsed or refractory low-grade or follicular, CD20-positive, B-cell non-Hodgkin lymphoma in 1997, and then for RA [7]. Off-label use of rituximab in SLE was first reported in 2002 and, since then, has been increasingly used in patients with SLE [8]. However, the advanced results of the LUNAR trial [9] showed that rituximab plus mycophenolate was not superior to mycophenolate in SLE patients with proliferative nephritis (types III/IV). Although definite conclusions must await full details of this trial, the negative preliminary results are discouraging [10]. This is in contrast to the good results for the off-label use of rituximab reported by various centers with long clinical experience in the management of SLE [11], [12], [13], [14], [15], [16], [17], illustrating the differences that occur between real-life and trials.
In this study, we present a pooled analysis of the efficacy of rituximab in real-life patients from European cohorts diagnosed with biopsy-proven lupus nephropathy who were treated with rituximab.
Section snippets
UK-BIOGEAS Registry
In January 2009, nine centers from UK and Spain specialized in the management of SLE patients created the UK-BIOGEAS Registry, a multicenter study devoted to evaluate the efficacy of the off-label use of rituximab in adult patients with lupus nephritis in a real-life setting. By December 2010, the database included 151 consecutive patients with lupus nephritis treated with rituximab. The inclusion criteria were: i) diagnosis of SLE based on the current classification criteria [18]; ii) adult
General description
A total of 164 patients (99 from the UK-BIOGEAS Registry and 65 from the literature search) fulfilled the inclusion criteria for the pooled analysis (Table 1). There were 145 females and 19 males, with a mean age at LN diagnosis of 32.3 years, a mean time of evolution of SLE until LN diagnosis of 8.1 years and a mean time of evolution of LN until renal biopsy of 5.8 years. Ninety-two (56%) patients were Caucasian, 46 (28%) Black, 22 (13%) Asian and four classified as “other”.
In 82 (50%) cases,
Discussion
SLE is not a benign disease. Patients with SLE have a 1.5 to 5-fold increased risk of mortality [29] and nearly 10% die within 10 years of the diagnosis [30]. Clinically, therapeutic decisions in SLE are based on personal experience and reported studies since there are no standardized therapeutic guidelines, with the exception of very recent EULAR proposals [31], [32]. The small number of RCTs in SLE may be explained by the low prevalence, the heterogeneous clinical presentation (often
Disclosure statement
The BIOGEAS Study group had received educational grants (2006–2008) from Roche and Abbott supporting the design and maintenance of the webpage www.biogeas.es. The financial support of Roche and Abbott was exclusively limited to maintaining the BIOGEAS webpage.
Take-home messages
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Rituximab in lupus nephritis (LN) currently seems to be good in real life, but bad in controlled trials.
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We present the results of the use of rituximab in 164 patients with biopsy-proven LN, the majority refractory to standard therapies, with a clinical response in two thirds of patients at both 6 and 12 months, and a rate of CR of 27% at 6 months rising to 30% at 12 months.
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We found a different rate of response according to the ISN/RPS histopathological classification, with a 4-fold higher rate of
Acknowledgments
Drs. Martinez-Berriotxoa and Ruiz-Irastorza are supported by the Department of Education, Universities and Research of the Basque Government. Dr. Vital is supported by a fellowship from the National Institute of Health Research, UK.
References (55)
- et al.
Refractory disease in Systemic Lupus Erythematosus
Autoimmun Rev
(2011) Outcomes of renal transplantation among patients with end-stage renal disease caused by lupus nephritis
Kidney Int
(2000)- et al.
Predictive factors of response to rituximab therapy in rheumatoid arthritis: What do we know today?
Autoimmun Rev
(2010) - et al.
Epidemiology and management of refractory lupus nephritis
Autoimmun Rev
(2011) - et al.
The administration of low doses of rituximab followed by hydroxychloroquine, prednisone and low doses of mycophenolate mofetil is an effective therapy in Latin American patients with active systemic lupus erythematosus
Autoimmun Rev
(2010) - et al.
Rituximab treatment of systemic lupus erythematosus in controlled trials and in clinical practice: two sides of the same coin
Autoimmun Rev
(2010) - et al.
How to improve morbidity and mortality in systemic lupus erythematosus
Rheumatology (Oxford)
(2000) - et al.
Outcomes in biopsy-proven lupus nephritis: evaluation of 190 white patients from a single center
Medicine (Baltimore)
(2010) - et al.
The long-term clinical course of systemic lupus erythematosus in end-stage renal disease
N Engl J Med
(1983) - et al.
Previous antimalarial therapy in patients diagnosed with lupus nephritis: influence on outcomes and survival
Lupus
(2008)