European LUpuS Inception-Cohort Developing initiATivE

PROTOCOL SYNOPSIS

• Introduction Systemic lupus erythematosus (SLE) is a complex autoimmune disease with diverse clinical manifestations. Despite recent therapeutic advances, challenges persist, including increased mortality, long-term complications, and impaired quality of life. We still use a step-up approach to treatment guided by EULAR recommendations although we know only around 50% of patients reach a low disease activity state within a year.

The establishment of a European inception cohort with a biobank aims to address these challenges by providing standardized data, particularly in the context of evolving treatment paradigms.

• Background and Rationale SLE's heterogeneity poses challenges, and global cohorts face variability in patient management and genetic diversity. A European inception cohort offers advantages, including homogeneity in treatment standards and genetic backgrounds, enhancing data reliability. Recent therapeutic approvals signal progress, with a shift towards a "treat-to-target" approach, underscoring the need for a more nuanced understanding of disease activity and response factors.
• Objectives The primary objective is to establish a European, multi-national, prospective, observational inception SLE cohort with a comprehensive biobank.

The study aims to assess the frequency of SLE patients achieving remission or low disease activity using novel criteria within specific timeframes.

Utilizing the biobank, the study aims to identify novel biomarkers associated with treatment response/non-response, SLE-related comorbidities, pain, fatigue, and genetic factors. These objectives include investigating soluble biomarkers, genetic associations, metabolites, and risk factor algorithms that contribute to understanding disease mechanisms, treatment responses, and the development of comorbidities.

• Study Design This European, multi-national, multi-centric, prospective, observational inception cohort involves follow-up visits at baseline, 3 months, 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years. The study design encompasses a main protocol, a biobanking module, and optional subprotocols to address specific research questions.
• Methods Adult patients with clinical diagnosis of SLE and fulfilling the 2019 ACR/EULAR criteria before initiation treatment are eligible. If treatment has been initiated, patients can still be included if it is less than six months since diagnosis and the patient has clinically and biochemically active disease (SLEDAI>6). Recruitment will take place over a two-year enrolment period and a five-year follow-up period, with an estimated 720 patients enrolled. Blood samples will be stored locally and later transferred to a centralized coordinating center. Clinical data, PROMs, blood, and urine will be collected at each visit.
• Perspective This protocol aims to propel SLE research forward, providing a robust foundation for understanding the disease, its treatment, and factors influencing patient outcomes. Through a collaborative, multi-national effort, this initiative endeavors to pave the way for personalized medicine in the management of systemic lupus erythematosus.
• Novelty To date, the SLICC SLE baseline cohort is the only existing international baseline cohort. It was initiated in 1998 and has generated significant new knowledge in the field of lupus over the past 25 years. The SLICC inception cohort was developed to better understand atherosclerosis, nervous system involvement, lupus nephritis and damage accumulation and their economic impact. It includes patients within 15 months of diagnosis and recruitment was completed in 2011. Since then, much progress has been made in the management of SLE. The re-enlistment of an inception cohort can help to assess the practical implementation and impact of new trends in diagnosis and treatment, as well as their effect on disease progression and outcome. ELUSIDATES aims to enroll patients immediately after diagnosis to ensure a true inception cohort. Ideally, patients will have no prior treatment or damage and can be followed for the first 5 years of the disease. In addition to clinical data, and in contrast to the SLICC inception cohort, biosampling will allow characterization of patients at the molecular level and analysis of biomarkers and predictive models.

Recruitment will be incentivised by allowing participating centres to submit their research sub-protocols, a strategy to ensure high recruitment rates.

Inclusion criteria

• Inclusion at clinical diagnosis of SLE (or strong clinical suspicion hereof) before initiating treatment (if treatment has been initiated, patients can still be included if it is less than six months since diagnosis and the patient has clinically and biochemically active disease (SLEDAI>6).
• Fulfilling the 2019 ACR/EULAR criteria for Systemic Lupus Erythematosus
• >18 years of age (adult onset SLE)
• Ability to provide informed voluntary consent.

Exclusion criteria

• Diagnosed with overlapping systemic autoimmune diseases other than secondary Sjögren's syndrome or antiphospholipid syndrome.
• Active treatment for malignancy at the time of enrolment, except for non-melanoma skin cancer or localized carcinoma in situ of the skin.