Abstract
Primary Sjögren syndrome (pSS) is a systemic autoimmune disease that is characterized by a triad of symptoms that affect all patients (dryness, pain and fatigue). In addition, systemic involvement can affect between one-third and one-half of patients. The management of patients with pSS has been negatively affected by a lack of effective treatments; however, knowledge of the epidemiology of pSS has increased, and advances in developing classification criteria, systemic disease activity scoring and patient-reported outcomes have been made during the past decade. Progress has also been made in understanding the mechanisms that underlie the pathogenesis of pSS, which has enabled a more targeted therapeutic approach to be taken. At present, therapeutic decisions rely on the evaluation of symptoms and systemic manifestations and are mostly formed on the basis of experience rather than evidence, and on similarities with other autoimmune diseases, although the 2019 management recommendations from EULAR are now being used to inform clinical management of pSS. This Review summarizes the available evidence for systemic treatments for pSS and includes discussions of advances in outcome assessment, the current evidence for DMARD use and an overview of promising future therapeutics.
Key points
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Currently available classic immunosuppressive drugs might be effective for treating some systemic manifestations of primary Sjögren syndrome (pSS), as is the case for other connective tissue diseases.
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Following the failure of the first randomized controlled trials (RCTs) in pSS, efforts are ongoing to define new therapeutic targets and new outcome measures.
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For the first time, two agents have met their primary outcome of improvement in systemic disease activity in RCTs in pSS: anti-B cell-activating factor receptor and anti-CD40 antibodies.
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Targeting B cells remains the most promising therapeutic approach for pSS.
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New outcome measures for RCTs aim to combine end points to assess all disease manifestations, including systemic activity, saliva and tears function, patient-reported outcomes and biological features.
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The work of the authors is supported by the Innovative Medicines Initiative 2 Joint Undertaking (NECESSITY grant agreement 806975).
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R.S. declares that she has received honorarium from BMS, Pfizer and UCB. G.N. declares that she has received honorarium from Lilly, Novartis and UCB. X.M. declares that he has received honorarium from BMS, Galapagos, Gilead, GSK, Novartis, Pfizer, Servier and UCB. X.M. has also received an unrelated research grant from OSE Immunotherapeutics.
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Glossary
- Xerostomia
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Oral dryness.
- Xerophthalmia
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Ocular dryness.
- Light zone
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An area of the germinal centre in which B cells depend on T cell help and are selected by competing for antigens presented by follicular dendritic cells.
- Dark zone
-
An area of the germinal centre that contains large centroblasts that are rapidly proliferating and undergoing somatic mutation.
- Focus score
-
The number of foci (dense aggregates of ≥50 mononuclear cells) per 4 mm2 over the whole glandular area of a salivary gland.
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Seror, R., Nocturne, G. & Mariette, X. Current and future therapies for primary Sjögren syndrome. Nat Rev Rheumatol 17, 475–486 (2021). https://doi.org/10.1038/s41584-021-00634-x
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DOI: https://doi.org/10.1038/s41584-021-00634-x
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