Clinical Efficacy and Safety of Baminercept, a Lymphotoxin β Receptor Fusion Protein, in Primary Sjögren's Syndrome

Clair, E. William St.; Baer, Alan N.; Wei, Chungwen; Noaiseh, Ghaith; Parke, Anne; Coca, Andreea; Utset, Tammy O.; Genovese, Mark C.; Wallace, Daniel J.; McNamara, James; Boyle, Karen; Keyes-Elstein, Lynette; Browning, Jeffrey L.; Franchimont, Nathalie; Smith, Kira; Guthridge, Joel M.; Sanz, Igñacio; James, Judith A.

doi:10.1002/art.40513

Cited by 73 publications

(39 citation statements)

References 37 publications

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“…Unexpectedly, 6 months of baminercept treatment failed to improve glandular dysfunction in patients with primary SS. Although not achieving expected treatment efficacy, the studies revealed, to some extent, the therapeutic effect of baminercept in LT/LIGHT-dependent pathways, suggesting that blocking LTβR signaling might be of therapeutic benefit at earlier stages (121). Both treatments resulted in decreased serum CXCL13 levels in patients with RA, but baminercept treatment was unable to diminish the serum levels of BAFF, LIGHT, or IP-10 compared to the placebo group (119,120).…”

Section: Discussionmentioning

confidence: 90%

Chronic Inflammation: A Common Promoter in Tertiary Lymphoid Organ Neogenesis

et al. 2019

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Tertiary lymphoid organs (TLOs) frequently develop locally in adults in response to non-resolving inflammation. Chronic inflammation leads to the differentiation of stromal fibroblast cells toward lymphoid tissue organizer-like cells, which interact with lymphotoxin α 1 β + 2 immune cells. The interaction initiates lymphoid neogenesis by recruiting immune cells to the site of inflammation and ultimately leads to the formation of TLOs. Mature TLOs harbor a segregated T-cell zone, B-cell follicles with an activated germinal center, follicular dendritic cells, and high endothelial venules, which architecturally resemble those in secondary lymphoid organs. Since CXCL13 and LTα 1 β 2 play key roles in TLO neogenesis, they might constitute potential biomarkers of TLO activity. The well-developed TLOs actively regulate local immune responses and influence disease progression, and they are thereby regarded as the powerhouses of local immunity. In this review, we recapitulated the determinants for TLOs development, with great emphasis on the fundamental role of chronic inflammation and tissue-resident stromal cells for TLO neogenesis, hence offering guidance for therapeutic interventions in TLO-associated diseases.

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Section: Discussionmentioning

confidence: 90%

Chronic Inflammation: A Common Promoter in Tertiary Lymphoid Organ Neogenesis

et al. 2019

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“…Figure 1 summarises the SLR results. Summary-of-finding tables were generated for RCTs (table 1),10 12–19 prospective cohort studies (table 2)20–37 and case-control studies (table 3). 38–42 For RCTs, the risk of bias (RoB) was assessed using the Cochrane RoB assessment tool (Cochrane Handbook for Systematic Reviews of Interventions V.5.1.0 March 2011 (available from: http://handbook.cochrane.org/)), and for uncontrolled studies, we used the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement checklist.…”

Section: Methodsmentioning

confidence: 99%

Efficacy and safety of topical and systemic medications: a systematic literature review informing the EULAR recommendations for the management of Sjögren’s syndrome

et al. 2019

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ObjectiveTo evaluate current evidence on the efficacy and safety of topical and systemic medications in patients with primary Sjögren syndrome (SjS) to inform European League Against Rheumatism treatment recommendations.MethodsThe MEDLINE, EMBASE and Cochrane databases were searched for case-control/prospective cohort studies, randomised controlled trials (RCTs) and systematic reviews.ResultsCurrent evidence in primary SjS patients fulfilling the 2002 criteria is based on the data from 9 RCTs, 18 prospective cohort studies and 5 case-control studies. Two Cochrane systematic literature reviews (SLRs) have reported that topical treatments for dry mouth and dry eye are safe and effective. Ocular cyclosporine A was safe and effective in two RCTs including 1039 patients with dry eye syndrome. Two Cochrane SLRs on serum tear drops and plugs showed inconsistency in possible benefits, both for symptoms and objective measures. Five RCTs reported significant improvements in oral dryness and salivary flow rates for pilocarpine and cevimeline. An RCT showed no significant placebo-differences for hydroxychloroquine 400 mg/day for the primary outcome (visual analogue scale (VAS) composite of dryness, fatigue and pain). We identified seven RCTs carried out in primary SjS patients. RCTs using infliximab, anakinra and baminercept found no placebo-differences for the primary outcomes. The two largest RCTs randomised 255 patients to receive rituximab or placebo and reported no significant results in the primary outcome (VAS composite), while prospective studies suggested efficacy in systemic disease.ConclusionThe current evidence supporting the use of the main topical therapeutic options of primary SjS is solid, while limited data from RCTs are available to guide systemic therapies.

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“…Preliminary results were presented at the 2015 ACR meeting in San Francisco. 47 Primary endpoint was improvement of pilocarpine-stimulated whole salivary flow and was not achieved. However, ESSDAI improved significantly more in the baminercept group than the placebo group.…”

Section: Germinal Centerlike Structures: a Promising Targetmentioning

confidence: 99%