Efficacy and safety of rituximab in the treatment of non-renal systemic lupus erythematosus: A systematic review
Introduction
Systemic lupus erythematosus (SLE) is an autoimmune rheumatic disease with protean manifestations in multiple organ systems. Current medical practice includes glucocorticoids, antimalarials and immunosuppressant (ISS) drugs to reduce disease activity and prevent flares. However, these treatments are not enough to control the disease. Some patients have several manifestations simultaneously and need an additional treatment to control general disease activity. Furthermore, some patients may have refractory organ-specific manifestations, such as arthritis, or life-threatening situations, such as neurological involvement. Currently, off-label use of rituximab has been used as an alternative on the basis that several abnormalities in SLE B cell populations have been identified and play a central role in the pathogenesis of SLE. Some studies have stressed the efficacy of rituximab in the treatment of most manifestations, with many of these studies focusing on nephritis [1], [2], [3], [4]. Previously, some systematic reviews tried to summarise the information concerning efficacy and safety of rituximab in the treatment of SLE [5], [6], but the data on the outcomes did not discriminate between studies that focused on nephritis and those that did not. In addition, specific outcomes relating to non-renal manifestations were not evaluated. In order to recommend rituximab, it would be useful to identify a profile of patients who are most likely to benefit from its use, particularly considering the recent approval of belimumab, which shows non-renal non-severe manifestations and flare-prevention effects. Both biologic treatments are not exclusive; the same patient may need them at some point.
Thus, the aim of this article was to systematically review the available literature regarding the efficacy and the safety of rituximab in the treatment of non-renal manifestations of SLE.
Section snippets
Methods
This study was performed by experts from the Evidence-based Medicine Study Group and the Systemic Autoimmune Diseases Study Group of the Spanish Society of Rheumatology. Initially, we conducted a systematic review on the efficacy and the safety of biologic and non-biologic ISS drugs in the treatment of non-renal SLE. The data about non-biologic ISS drugs have been recently published [7]. Now, we present data on rituximab.
Results
The literature search produced 3410 articles, of which 186 underwent full review and 24 met the inclusion criteria. We identified 2 additional studies by hand search (Fig.). The evidence table including the population studied, interventions and outcomes with their definitions is available in Appendix 3. The excluded studies and reasons for exclusion are shown in Appendix 4.
The 26 studies included 1 RCT and its exploratory analysis [10], [11], 2 open-label studies [12], [13] and 22 cohort
Discussion
We conducted a systematic review of the literature to analyse the efficacy and the safety of rituximab in the treatment of non-renal SLE. Rituximab has an off-label use, which is mainly used to treat patients with either life-threatening situations or severe involvement refractory or intolerant to standard therapy. In this sense, the rituximab studies reveal as much information about the overall disease activity as about organ-specific manifestations.
In our systematic review, we found
Conclusion
Rituximab could be considered a safe and effective short–medium term option in the treatment of non-renal SLE, reducing disease activity, steroid doses and anti-DNA levels and increasing complement levels. However, disease relapses are significant. Regarding particular involvements, the best response is in arthritis and autoimmune thrombocytopaenic purpura. We cannot draw conclusions about autoimmune haemolytic anaemia and neuropsychiatric manifestations because there are too few reliable
Acknowledgements
We want to thank the experts from the Systemic Autoimmune Diseases Study Group of the Spanish Society for Rheumatology (EAS-SER) for suggesting the research question and for their valuable and constructive suggestions during the development of this research work.
We would also like to express our very great appreciation to Ms. María Piedad Rosario-Lozano (Research Unit of the Spanish Society of Rheumatology), who checked the search strategies.
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2021, Revista Colombiana de ReumatologiaCitation Excerpt :Additionally, polyarthritis, high disease activity (SLEDAI ≥ 10), and increased anti-dsDNA have been suggested as predictors of response to belimumab.85 Targeting CD20 with rituximab has been endorsed in several centers where it is used as an off-label therapeutic option in SLE, mostly for refractory renal disease, but also for other organ manifestations when conventional treatment has failed, including severe lupus polyarthritis.86,87 Literature data suggests the efficacy of abatacept to treat SLE patients with joint involvement.14
From the Systemic Autoimmune Diseases Study Group of the Spanish Society for Rheumatology (EAS-SER).
Role of the funding source: This study was supported by the Spanish Foundation of Rheumatology (FER) with an unrestricted educational grant from Roche Farma, SA. The FER and Roche Farma had no role in the extraction and interpretation of data or in the draft of the manuscript. All authors had full access to all the data included in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Dr. J.M. Pego-Reigosa was supported by the Grant 316265 (BIOCAPS) from the European Union 7th Framework Programme (FP7/REGPOT-2012-2013.1).
Competing interest: Dr. Fernandez-Nebro reports grants and personal fees from Pfizer, grants and personal fees from Roche, personal fees from BMS, personal fees from MSD and personal fees from Abbvie, outside the submitted work. Dr. López Longo reports grants and personal fees from GKS, personal fees from ABBVIE, non-financial support from UCB, non-financial support from MSD and non-financial support from Roche, outside the submitted work. Dr. Caliz reports grants, personal fees and non-financial support from Roche, personal fees and non-financial support from MSD and personal fees and non-financial support from Pheizer, outside the submitted work.