Recommendations and metaanalysesEfficacy and safety of biological DMARDs modulating B cells in primary Sjögren's syndrome: Systematic review and meta-analysis
Introduction
Sjögren's syndrome is a systemic autoimmune disease, characterised by lymphoplasmocytic infiltration of exocrine glands leading to a progressive functional impairment. Fatigue, articular pain, ocular and oral dryness are the main symptoms and these often reduce quality of life. However, for about one third of the patients, the disease is accompanied by systemic manifestations that can be serious and involve the musculoskeletal system, nervous system, lungs, kidneys, skin and blood vessels skin [1], [2]. Also about 5 to 10% of pSS patients are estimated to develop a B-cell lymphoma [3], [4].
Increasing evidence supports that B-cell hyperactivity plays a central role in pSS physiopathology as reflected by the presence of autoantibodies (rheumatoid factor (RF), anti-SSA/Ro and anti-SSB/La), cryoglobulins and hypergammaglobulinemia [5]. Cytokines playing a key role in B-cell homeostasis, such as BAFF and IL6 [5], are increased in this disease. Until today, the treatment of the Sjögren syndrome has been mainly based on symptomatic measures. Recently, guidelines have been published and the use of rituximab was considered as a therapeutic option in selected clinical settings for oral and ocular dryness and for certain systemic manifestations [6]. However, a recent review [2] suggests that rituximab should probably not be used in pSS, except in patients with severe disease and no other treatment options. Studies on rituximab and other B-cell targeted therapies showed conflicting results and their place in the management of pSS remains controversial. [7]. A recent meta-analysis of the results of randomised trials evaluating rituximab was performed [8]. However, this study has many methodological and statistical limitations.
The purpose of this systematic review and meta-analysis was to analyse and summarise the evidence on b-DMARDs modulating B cells for the main clinico-biological manifestations of primary Sjögren syndrome (sicca symptoms, fatigue, pain, ESSDAI) for adults.
Section snippets
Methods
This study was conducted in line with the guidelines of the Cochrane Collaboration and our findings are reported according to the Preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. The following sources were used: the Cochrane, Medline (from 1946) and Embase databases (from 1947) and the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) annual meetings’ databases up to April 12, 2016. The keywords used were Sjögren's
Literature research and study characteristics
The literature retrieving strategy is shown in the flowchart (Fig. 1). There were 416 potentially relevant papers and two ACR abstracts. After screening the title and reading the abstract and full-length article, 16 published articles [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [28] and two abstracts [25], [26] with a total of 636 patients were included in this review. The highest-quality studies, i.e. the randomised controlled trials, were selected
Discussion
Rituximab has shown encouraging results in open studies and two randomised controlled trials regarding the reported symptoms. However, our meta-analysis showed that neither statistical nor clinical significance was found in pooled results. The limits of our meta-analysis were the heterogeneity of endpoints between articles. Therefore, we could combine the results of two or three different studies for each criterion assessed. Moreover, the number of patients in each study was low, notably
Disclosure of interest
Supported by AbbVie: AbbVie France pharmaceutical company provided logistic support by organizing a meta-analysis methods workshop but played no further role in the project. No fund was received to carry out this study.
Pr Lukas, MD, PhD, has received honoraria from Roche-Chugai and UCB less than 8000€.
Pr Gaujoux-Viala, MD, PhD, has received honoraria from Roche-Chugai and UCB less than 8000€.
Pr Combe, MD, PhD, has received honoraria from Roche-Chugai and UCB less than 8000€.
Pr Morel, MD, PhD,
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Cited by (28)
Updates in diagnostics, treatments, and correlations between oral and ocular manifestations of Sjogren's syndrome
2022, Ocular SurfaceCitation Excerpt :The same review found anti-B cell drugs such as epratuzumab and belimumab, fusion protein etanercept, costimulatory signal inhibitor abatacept and CD40 inhibitor CFZ533 are promising alternatives which warrant future studies. Conversely, another meta-analysis showed rituximab is not effective in treatment of patients with pSS and suggested investigation of efficacy of other B-cell-targeted therapy such as belimumab and epratuzumab in treating SS [73]. In view of the mixed evidence supporting rituximab as well as its serious side effects such as increased risk of infection and reactivation of hepatitis B, the use of rituximab for oral dryness is debatable and is not recommended by ACR/EULAR [61,74].
Posterior scleritis with anti-neutrophil cytoplasmic antibody-associated vasculitis utilizing rituximab therapy to maintain remission: A case report
2022, American Journal of Ophthalmology Case ReportsCitation Excerpt :In Japan, the combination therapy of CYC and GCs has been a gold standard to achieve remission in AAV.14 However, the frequency of treatment-associated side effects, such as infectious complications, cardiovascular diseases, myelosuppression, malignancy, and infertility, remains high.15–17 RTX is a cytotoxic monoclonal antibody, which depletes B cells upon CD20 binding.
Sjögren’s Syndrome Dry Eye Disease
2022, Dry Eye DiseaseP2Y<inf>2</inf> receptor antagonism resolves sialadenitis and improves salivary flow in a Sjögren's syndrome mouse model
2021, Archives of Oral BiologyCitation Excerpt :It would be interesting to determine whether P2Y2Rs are specifically expressed in MZ B cells and how P2Y2R antagonism affects this population of B cells in SS models. Despite the body of evidence implicating B cells in SS pathogenesis, B cell depletion using Rituximab has been largely ineffective as a therapeutic strategy (Letaief et al., 2018), possibly due to co-depletion of anti-inflammatory B regulatory cells that are elevated in human SS patients (Mielle et al., 2019). Another explanation for the lack of Rituximab efficacy may be that it fails to deplete long-lived plasma cells (Mahevas, Michel, Weill, & Reynaud, 2013; Rosenberg et al., 2016).
Alleviating effect of paeoniflorin-6′-O-benzene sulfonate in antigen-induced experimental Sjögren's syndrome by modulating B lymphocyte migration via CXCR5-GRK2-ERK/p38 signaling pathway
2020, International ImmunopharmacologyCitation Excerpt :Increasing evidence supports the observation that B-cell hyperactivity is a critical pathogenetic mechanism of pSS. B cells stimulate T cells, secrete inflammatory cytokines and produce autoantibodies, such as rheumatoid factor, anti-Sjögren's syndrome-related antigen A/Ro (anti-SSA/Ro) and anti-Sjögren's syndrome-related antigen B/La (anti-SSB/La) which are pro-inflammatory [4]. Approximately about 5–8% of pSS patients show an increased susceptibility of developing B-cell lymphoma, and aberrant B-cell profiles have found in the peripheral blood of some pSS patients [5].
Corneal and scleral involvement in inflammatory rheumatic disease: Rheumatologists and ophthalmologists exchanging views
2019, Joint Bone SpineCitation Excerpt :Pilocarpine increases salivary output but has little effect on ocular dryness. Disease-modifying antirheumatic drugs (DMARDs) have not been proven effective on primary or secondary sicca syndrome [4]. In moderate-to-severe cases, topical ciclosporin in concentrations of 0.05% to 2% can be given, in combination with 20% autologous serum.