SLE Prospective Observational Cohort Study (SPOCS)
Research type
Research Study
Full title
Systemic Lupus Erythematosus (SLE) Prospective Observational Cohort Study (SPOCS)
IRAS ID
228393
Contact name
David Isenberg
Contact email
Sponsor organisation
IQVIA
Duration of Study in the UK
4 years, 9 months, 16 days
Research summary
Research Summary
Systemic lupus erythematosus (SLE) is a chronic, multisystem, and often progressive autoimmune disorder with multiple manifestations. Although the etiology remains unknown much has been discerned about the pathogenesis of SLE with genetic, immunologic, hormonal, and environmental factors playing important roles. Whereas the survival rate for patients with SLE has significantly improved, mortality remains high compared to the general population with an approximately two-fold increased risk of all cause mortality.
Current therapies for SLE include anti-inflammatory drugs, antimalarial, corticosteroids, immunosuppressive agents and biologics. While there has been advancement in clinical research activities in SLE, the rewards have been minimal with only one new drug approved in the last many decades. Strategies for drug development have targeted different components of the immune system.
Type I interferon (IFN) is thought to play a central role in the pathogenesis and disease course of SLE. While clinical trials of alpha interferon inhibitors were met with varied results, recent results of the phase II study of a type I IFN receptor antibody were positive. Furthermore, patients with high type I interferon gene signature at study entry were observed to have greater effect sizes than patients with low type I interferon gene signatures. However there is inadequate information on the association of type I interferon gene signature with disease severity and activity.
The rationale for the SLE Prospective Observational Cohort Study (SPOCS) is to describe the relationship between patient characteristics, clinical features, healthcare resource utilisation, and health-related quality of life in moderate-to-severe SLE patients assessment score without the inclusion of points attributable to any urine or laboratory results. SPOCS will also describe the distribution of the type I interferon gene signature and how its longitudinal expression in SLE patients relates to disease activity and outcomes.Summary of Results
SPOCS enrolled 826 patients with moderate to severe SLE (Systemic lupus erythematosus) across North America, Europe and Australia. Approximately two-thirds of enrolled patients at baseline expressed high type I IFN (Interferon) gene signature. IFN gene signature status was relatively stable over time, with most of the population remaining in the same category over time. SLEDAI-2K (Systemic Lupus Erythematosus Disease Activity Index 2000), PGA-VAS (Physician Global Assessment-visual analogue score), and PtGA (patient global assessment) values reduced during early follow-up but remained stable for the remainder of the follow-up. Disease activity patterns over time (as assessed by SLEDAI-2K, PGA-VAS, and PtGA) showed no clear differences between patients expressing high and low type I IFN gene signature. Nearly 20% of patients had new organ damage after 12 months. Organ damage data (SLICC/ ACR DI-Systemic Lupus International Collaborating Clinics/American College of Rheumatology) showed higher damage in patients expressing low type I IFN gene signature compared to high type over each time point. Patients taking OCS (oral corticosteroids) average daily dose of >7.5 mg/day at baseline was associated with 89% increased risk of organ damage during the 3-year follow-up as compared to patients taking OCS average daily dose of >0 - ≤7.5 mg/day at baseline. Less than 20% of patients achieved LLDAS (Lupus Low Disease Activity State) and less than 15% achieved remission during the entire 36 months of follow-up. The percentage of patients achieving LLDAS or remission during follow-up did not differ between type I IFN gene signature groups except at 24-month follow-up, where a significantly higher percentage of patients achieved LLDAS in the low type I IFN gene signature group than in the high group Patients with high type I IFN gene signatures at baseline had a higher probability of moderate/severe flares and a higher number of SLE-related hospitalizations during follow-up.
The increase in mean daily OCS dose in the first 6 months was maintained through 36 months despite standard therapy, stable antimalarial use, and moderate increases in use of biologics and immunosuppressants. The proportion of OCS use was largely stable over time, those on OCS>7.5 mg/day increased initially and then declined but did not return to the baseline level. Patients with IFNGS-high status used more immunomodulatory therapy compared with those with IFNGS-low status. In general, patient-reported HRQoL measured by SF-36 V2, FACIT-F, EQ5D-5L and LupusQoL showed better QoL measures in patients expressing high type 1 IFN signatures compared to those expressing low type across each timepoint.
Overall, SPOCS provided a wealth of real-world data on SLE patients and their outcomes over time.REC name
West Midlands - Edgbaston Research Ethics Committee
REC reference
17/WM/0250
Date of REC Opinion
23 Jun 2017
REC opinion
Favourable Opinion