Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a relapsing and remitting course that can be life threatening. Women of childbearing age are at highest risk of developing SLE, and SLE is more common in ethnic minority populations. While treatment advances have reduced mortality in SLE, patients still experience symptoms including pain, joint swelling, rashes and fatigue, impaired quality of life, and long-term morbidity. The clinical management of SLE is complex, as the disease is of unknown aetiology and has a highly heterogeneous and unpredictable disease course. Given the multi-system involvement in SLE, a multidisciplinary approach to management of SLE involving physicians (i.e. rheumatologists, immunologists, nephrologists), and nursing and allied health professionals is recommended. Treatment decision-making to minimise symptoms, the risk of relapse and adverse effects of immunosuppressive therapy remains a major challenge. There is a paucity of high-quality evidence to guide practice, and clinical practice guidelines on the care of patients with SLE are variable in terms of the quality and practice recommendations. The evidence on the patient experience, perspectives, and priorities for healthcare and research are also limited, and thus their needs and concerns may not be adequately addressed. Addressing these gaps in the evidence may explain some of the unwarranted variation in the management of SLE that is apparent across and within medical specialities and inform the delivery of patient-centred care, and ultimately improve clinical and quality of life outcomes in people with SLE. The first part of this thesis contains a comprehensive and systematic review of international clinical practice guidelines on the diagnosis, monitoring and treatment of SLE (Chapter 2), and a systematic review and meta-analysis of benefits and harms of different immunosuppressive treatments in people with biopsy-proven proliferative lupus nephritis (Chapters 3 and 4). These studies assess and synthesise the totality of the available evidence to guide the management of people with SLE and lupus nephritis. In Chapter 2, I assessed the scope, quality, and consistency of international clinical practice guidelines on the diagnosis, monitoring, and treatment of SLE. I conducted a comprehensive search, appraised, and synthesised all available guidelines. There was substantial variability across guidelines, particularly in terms of scope and methodological rigour. The recommendations were largely consistent, but discrepancies were observed in specific clinical situations, including the duration of maintenance therapy in patients with lupus nephritis. In Chapter 3, I systematically reviewed and conducted pairwise meta-analyses of all randomised controlled trials comparing any induction therapy or maintenance therapy for biopsy-proven proliferative lupus nephritis. Compared to intravenous cyclophosphamide, mycophenolate mofetil may be as effective in inducing disease remission, while mycophenolate mofetil in combination with tacrolimus may improve the induction of disease remission. The most effective maintenance therapy was mycophenolate mofetil. In a complex condition such as lupus nephritis, there are several treatment options available, but not all therapies have been directly compared within trials. In Chapter 4, I conducted a network meta-analysis to compare all induction and maintenance therapeutic strategies of proliferative lupus nephritis using direct and indirect evidence to rank treatments based on their efficacy and safety. The evidence for induction therapy, based on mortality and adverse renal outcomes is uncertain, but when added to corticosteroids, mycophenolate mofetil or calcineurin inhibitors or their combination are superior to intravenous cyclophosphamide in the induction of disease remission. The first part of this thesis (Chapters 2-4) demonstrated the inconsistency of clinical practice guidelines to direct the diagnosis, monitoring, and treatment of people with SLE. In addition, the systematic reviews and meta-analysis of immunosuppressive therapy for lupus nephritis showed considerable uncertainty in treatment effects across interventions as trials were often short in duration and were inadequately powered to detect events in the clinically important outcomes. In Chapter 5, the attitudes and perspectives of immunologists, nephrologists, and rheumatologists towards the management of SLE were examined; other medical specialities, nurses and allied health professionals are involved in the care of patients with SLE. However, their experiences and perspectives were not examined as part of this thesis. I conducted semi-structured interviews with 43 specialists from 19 institutions across Australia and identified the uncertainty associated with the management of SLE because of the ill-defined aetiology, the lack of consistent and implementable evidence, and fragmented speciality care. To overcome these challenges specialists’ translated evidence from similar diseases, anchored to their clinical training and sought to break down speciality silo structures by collaborating across medical disciplines. The third part of this thesis focuses on identifying the experiences and priorities of adolescent and young adults with SLE (Chapters 6 and 7). The studies in Chapters 6 and 7 involved the same patients from NSW and were conducted concurrently. In Chapter 6, the perspectives and experiences of adolescents and young adults with SLE were examined through focus groups and semi-structured interviews. Five themes were identified: marring identity, restricted major life decisions, multifaceted confusion and uncertainty, resentment of long-term treatment, gaining resilience and coping capacities. These themes highlighted that the uncertainty of the prognosis of SLE limited the physical and social capacities of young patients, and restricted their personal and career goals. To overcome these challenges and to maximise their participation in social, school and work life, young patients developed resilience, improved their capacity for self-management and relied on their social support networks. Chapter 7 is a mixed-methods study with 26 adolescents and young adults with SLE who identified and prioritised healthcare needs and research topics, and described the reasons underpinning their priorities. Young patients with SLE value comprehensive and coordinated care, they prioritised research that alleviates the anxiety associated with this remitting-relapsing disease and research that improves patients’ social acceptance among their peers. This thesis generated novel data based on a systematic review of clinical practice guidelines and meta-analysis of randomised controlled trials for clinicians and patients to make a decision based on the totality of the available evidence. Trials of longer duration with larger study populations are required to further support decision making, the use of registry-based randomised trials may help clarify the risks and eventual harms of treatments. The comprehensive and in-depth understanding of the perspectives of patients with SLE and their clinicians, described in this thesis, highlights the need to address anxieties relating to the uncertainty of disease prognosis, to increase patient’s disease-related knowledge to improve their capacity for self-management, and to improve integrated multidisciplinary care. These findings may inform strategies to optimise care and lead to improved health and quality of life outcomes for people with SLE.