Ab0815 Global Burden of Sjogren’s Disease (Sjd): Findings From a Systematic Literature Review (Slr) of Humanistic and Clinical Outcomes

Background: Sjogren's (SjD) is a systemic autoimmune disease characterized by glandular dysfunction, often with the involvement of other extra glandular organs. Two indexes measure systemic effects (ESSDAI) and patient symptoms (ESSPRI) of SjD, while other outcomes and humanistic scales measure inflammation and impact on specific organs. Limited information is available summarizing the known literature on the impact of SjD on humanistic burden and clinical outcomes, whether available treatments can alleviate the humanistic/clinical burden of SjD, and whether more advanced disease impacts patient health-related quality of life (HRQoL). Objectives: To characterize the humanistic burden associated with SjD and provide a comprehensive overview of the published evidence on available treatments for SjD. Methods: The SLR followed PRISMA guidelines; searches were conducted in key databases to identify humanistic, clinical, and real-world evidence (RWE) studies in SjD with no restriction on geography. Humanistic data was identified from the last 10 years; clinical and RWE data was identified from database inception. Conference proceedings from the last 3 years, health technology assessment (HTA) databases, clinicaltrials.gov, and bibliography searches were used to supplement the search. Results: Three hundred and fifty-two reports for 221 studies (157 humanistic, 43 clinical, 32 RWE) fulfilled the PICOS criteria. Included studies were from North America (n=23), South America (n=8), Europe (n=97), Africa (n=2), Middle East (n=27), Pacific Islands (n=1), Asia (n=40), and international/other (n=23). When compared to healthy controls (sample size 25-304), patients with primary SjD reported significantly worse HRQoL as measured by SF-36 (n=7), OHIP-14 (oral health; n=4), XI (dryness; n=3), FSS (fatigue; n=1), HADS-A (anxiety; n=4), and PSQI (sleep; n=1). Subgroup analysis revealed that patients with menopause reported worse sexual function (FSFI), patients who were pregnant or had anxiety or depression reported worse eye-related health (OSDI), patients with greater fatigue had more anxiety (HADS-A), and patients with oral burning sensations, lower salivation, and oral lesions reported worse oral health (OHIP-14). Phase 3 studies (n=6) assessing hydroxychloroquine (n=2), rituximab (n=2), and abatacept (n=2) were identified in patients with primary SjD (abatacept-treated patients reported ESSDAI scores ≥5); no treatment led to significant improvements in ESSDAI or ESSPRI scores (sample size 26-187). Rituximab significantly improved unstimulated saliva production in patients with primary SjD at 48 weeks follow-up, not 24 weeks; hydroxychloroquine and abatacept significantly reduced biomarker expression including IgM (hydroxychloroquine; n=1), IgG (n=2), ESR (hydroxychloroquine; n=1), and CXCL12 (abatacept; n=1). Evidence from RWE studies on patients with primary SjD (sample size 10-17) suggests that treatment with rituximab is associated with lower ESSDAI (n=2), ESSPRI (n=2), ESR (n=1), and RF (n=1). Hydroxychloroquine was associated with improved ESSDAI (n=1), ESSPRI (n=2), IgA (n=1), IgG (n=2), and Schirmer's test scores (n=2) in patients with primary SjD (sample size 14-383). Abatacept was associated with improved Schirmer's test scores (n=1) in patients with secondary SjD but did not significantly impact salivary flow rates (n=1) or IgG levels (n=2) in patients with primary or primary/secondary SjD respectively (sample size 11-36); ESSDAI and ESSPRI were not reported. Conclusion: SjD significantly impacts patient HRQoL compared to healthy controls. Patients with greater symptom burden (ESSPRI ≥5) report significant impacts on their HRQoL related to dryness, fatigue, depression, and anxiety. Phase 3 clinical trials have so far not revealed treatments that can adequately address HRQoL or the burden of illness as measured by ESSPRI and ESSDAI. Differences between clinical and RWE studies may be explained by the heterogeneous nature of RWE studies, small sample sizes, and varied follow-up times. REFERENCES: NIL. Acknowledgements: This work was funded by Amgen (formerly Horizon Therapeutics). Disclosure of Interests: Ann Xi Owns stock for Amgen Inc (formerly of Horizon Therapeutics), Employee of Amgen (formerly Horizon Therapeutics), Elizabeth Crane Owns stock for Amgen Inc (formerly of Horizon Therapeutics), Employee of Amgen (formerly Horizon Therapeutics), Ilias Alevizos Owns stock for Amgen Inc (formerly of Horizon Therapeutics), Employee of Amgen (formerly Horizon Therapeutics), Rhiannon I. Campden Employee of Cytel who was contracted by Amgen (formerly Horizon Therapeutics) for the purpose of this work, Deepika Thakur Employee of Cytel who was contracted by Amgen (formerly Horizon Therapeutics) for the purpose of this work, Haridarshan Patel Owns stock for Amgen Inc (formerly of Horizon Therapeutics), Employee of Amgen (formerly Horizon Therapeutics).