Dr Shereen Oon

There are few consensus-based treatment guidelines for Systemic Lupus Erythematosus (SLE). The goal of our project is to develop an evidence-based treatment algorithm for SLE, taking into account patient and physician preferences, and which draws on understanding of factors that influence treatment decision in this disease. There are, broadly, three steps involved in completing this project – firstly, understanding current practice and the current evidence-base regarding SLE treatments; secondly, understanding the patient, physician and other factors that influence treatment decisions in SLE; and finally combining knowledge gained from fulfilling the first two steps into the development of a patient and physician-centered, evidence-based treatment algorithm for SLE. It is hoped that development of such an algorithm, applied to routine clinical practice, will lead to improved treatment outcomes for patients with SLE.

In order to gain a better understanding of current practice, and the current evidence-base regarding SLE treatments, we are currently performing systematic reviews of treatment for each different SLE organ system involvement. We anticipate that these will be completed by the end of 2018, and submitted for publication. We have performed a systematic review of recent phase 3 clinical trials for SLE, which has been published in Seminars in Arthritis and Rheumatism, and presented at the American College of Rheumatology Annual Scientific Meeting in 2017. This study showed that few of the novel treatments tested in phase 3 clinical trials for SLE were successful in meeting their primary trial endpoints, however there was often benefit seen in biologic parameters, and in secondary clinical endpoints, in particular, in decreasing the need for the use of steroids. This study also added to the available literature suggesting that a chosen outcome measure can influence study success. To this end, we have also undertaken a post hoc analysis of a novel lupus disease remission outcome measure, the Lupus Low Disease Activity State (LLDAS), which was pioneered by the Asia Pacific Lupus Collaboration, led by Australian rheumatologists, in the pivotal phase 3 clinical trials of belimumab, the only phase 3 trials to meet their primary endpoints. We have found that the LLDAS is able to differentiate those who responded to belimumab from those who did not, but that it is a more stringent outcome measure than that used in the original trial. More stringent endpoints could have a potential benefit of being able to differentiate novel drugs with more robust effects. On the subject of outcome measures in SLE, we are also engaged in collaborative work with lupus experts in the United States, to develop a better understanding of the influence of laboratory parameters on the Physician Global Assessment (PGA) score in SLE. We have submitted work on the LLDAS in belimumab studies, and laboratory measures influence on the PGA, to be presented at the upcoming American College of Rheumatology Annual Meeting later this year.

With regard to understanding factors which influence treatment decisions in SLE, we are currently collaborating with Korean lupus experts to survey rheumatologists with expertise in treating lupus throughout the Asia-Pacific, on infrastructural influences on treatment, and also experts’ personal treatment preferences. We anticipate results from this research by the end of year, and to present the research at the upcoming 13^th International Congress on SLE in early 2019.

We plan to continue this research over the next 2-3 years, and have plans to survey patients throughout the Asia-Pacific region on their preferences regarding treatment, in early 2019, and to use data from the Asia–Pacific Lupus Collaboration on SLE database to gain an understanding of current treatment practices throughout the region. Thereafter, we plan to convene a patient-physician roundtable to formulate the treatment algorithm, and pilot-test it in lupus clinics at St Vincent’s Hospital and the Monash Medical Centre.

We would like to thank Arthritis Australia for providing this Fellowship, so that Dr Oon could carry out this research, which we hope will improve understanding and outcomes of SLE treatment.