A Lupus expert, Professor Ian Bruce of the University of Manchester, discusses a UK-wide consortium effort to disentangle the complexity of Lupus in order to define patient subgroups that will derive benefit from existing treatments.
The University of Manchester leads the UK-based consortium. Are there benefits from routine treatments or therapies that “failed” in previous clinical programs?
Systemic Lupus Erythematosus (SLE)
Systemic Lupus Erythematosus (SLE) is a chronic multisystem autoimmune condition that can affect a range of organs and tissues, including the joints, skin, kidneys, and brain. SLE affects one in 4,000 individuals in the UK and has a strong (10:1) female: male preponderance. African, Indo-Asiana Asian patients face greater risk.
Presently there are limited options for SLE treatment including antimalarial drugs, glucocorticoids and conventional immunosuppressive, most of which are off label. Only one drug (belimumab-Benlysta) since 1959 has been licensed for the treatment of SLA. Over, this treatment is used selectively on a “trial and effort basis.” According to this report from Professor Bruce new biologic therapies such as rituximab and belimumab, while targeting specific immune processes, produce response rates at 60% at best. Significant problems persist and of course, SLE can turn deadly.
An MRC (Medical Research Council)-funded UK consortium is known as the Maximizing SLE ThERapeutic Potential by Application of Novel and Stratified approaches (MASTERPLANS) is led from the University of Manchester by Professor Ian Bruce, Professor of Rheumatology. Made up of nine universities, 10 industry partners and participation from patient collaborators associate with Lupus UK, an exciting new collaborative model is now in place to identify lupus therapy response predictors.
Back to the Future
By going back in time to re-analyze previous SLE clinical trials while also assessing existing cohort data, the MASTERPLAN consortium seeks to identify factors that predict response or improvement in SLE.
The MASTERPLAN team seeks to establish A) which factors predict improvement in SLE in general and B) which are related to specific treatment regimes. The consortium is staffed with a bunch of statisticians and methodologists to help solve the stratification treatment challenges that lie ahead.
The British Isles Lupus Assessment Group Biologics Register (BILAG-BR) is a UK-wide prospective observational cohort study assessing the long-term safety and effectiveness of new treatments in SLE. The BILAG Biologics Prospective Cohort is a prospective observational cohort study of patients with SLE who are starting treatment with a biologic drug or a conventional, non-biologic therapy. The study aims to recruit 220 patients into the biologic treatment group and a further 220 patients into the conventional, non-biologic therapy cohort.
The aim of the BILAG BR is to ascertain whether using biologics in the routine treatment of SLE is associated with an increased risk of hospitalization for infection, compared to SLE patients with similar disease activity receiving conventional therapies. The secondary purpose of the BILAG Biologics Prospective Cohort is to determine the long-term efficacy of biological therapies in the treatment of SLE.
This prospective cohort study will recruit an exposed cohort of patients with SLE treated with biological therapies and an unexposed cohort of patients with similar disease characteristics but exposed only to conventional non-biological therapies. Comprehensive data will be collected at baseline, from the clinic team and the patient, including data on disease diagnosis and activity, risk factors for infection and routine laboratory results. Follow-up data will be collected at 3, 6, 12, 24 and 36 months to include any changes in medications, adverse events, hospitalizations for infections, disease activity and quality of life along with biological samples for biomarker analysis.
Dr. Ian Bruce, Professor of Rheumatology, University of ManchesterSource: Open Access Government