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Dr Benjamin Parker, Prof I Bruce
No more applications being accepted
About the Project
The British Isles Lupus Assessment Group Biologics Register (BILAG-BR) is a national, multicentre, prospective cohort study established in 2010 to monitor the safety and efficacy of biologics in SLE in a real-world lupus cohort, with a prime focus on longer term safety. Initially established as a collaborative effort across 10 BILAG centres, the study now recruits nationwide from all UK centres prescribing biologic therapy for patients with SLE with more than 500 biologic-treated patients contributed data to date. In the UK, access to rituximab (RTX) is facilitated through an NHS England Interim Policy written in 2013. Continued access relates in part to demonstration of safety and efficacy in this setting using BILAG-BR data.Similar arrangements were recommended by NICE for the use of belimumab in SLE, as part of a unique managed access arrangement with NHS England.
The primary outcome of BILAG-BR is incidence of serious infections in RTX treated patients, but the size of the cohort also allows efficacy and predictors of response to RTX to be explored further. Our recent work suggests ~10% of RTX treated patients suffered a serious infection in a provisional analysis of 270 patients. In addition, many SLE patients develop hypogammaglobulinaemia after RTX, possibly due to B cell depletion but also due to exposure to sequential immunosuppressive therapies, including steroids. Several of these patients proceed to suffer with infections and a smaller number proceed to require immunoglobulin replacement therapy. However the precise prevalence and causes of this in patients with SLE is largely unknown.
Given that safety of therapies is a key predictor of adherence, response, and overall efficacy of a therapy a better understanding of the prevalence and predictors of serious infections and other adverse of interests will inform future use of RTX in SLE. The student will lead on examining overall safety of biologics in SLE, using BILAG-BR data and linking with the MRC-funded MASTERPLANS consortium, with a focus on serious infections and related adverse events. This stratified medicine approach to biologic therapy in SLE should improve our understanding of predictors of response to these drugs, factors which are increasingly important given the heterogeneous nature of the disease and variable response to all therapies.
If successful, the student will join the CTD theme of Manchester BRC, an established research team with extensive experience of experimental medicine research in SLE, and have the opportunity to experience the tertiary clinical service at neighbouring Kellgren Centre for Rheumatology at Manchester Royal Infirmary. Extensive support will be given in laboratory technique, data cleaning, adverse event coding, statistical analysis and a clear route through to translation via BILAG group.
The primary outcome of BILAG-BR is incidence of serious infections in RTX treated patients, but the size of the cohort also allows efficacy and predictors of response to RTX to be explored further. Our recent work suggests ~10% of RTX treated patients suffered a serious infection in a provisional analysis of 270 patients. In addition, many SLE patients develop hypogammaglobulinaemia after RTX, possibly due to B cell depletion but also due to exposure to sequential immunosuppressive therapies, including steroids. Several of these patients proceed to suffer with infections and a smaller number proceed to require immunoglobulin replacement therapy. However the precise prevalence and causes of this in patients with SLE is largely unknown.
Given that safety of therapies is a key predictor of adherence, response, and overall efficacy of a therapy a better understanding of the prevalence and predictors of serious infections and other adverse of interests will inform future use of RTX in SLE. The student will lead on examining overall safety of biologics in SLE, using BILAG-BR data and linking with the MRC-funded MASTERPLANS consortium, with a focus on serious infections and related adverse events. This stratified medicine approach to biologic therapy in SLE should improve our understanding of predictors of response to these drugs, factors which are increasingly important given the heterogeneous nature of the disease and variable response to all therapies.
If successful, the student will join the CTD theme of Manchester BRC, an established research team with extensive experience of experimental medicine research in SLE, and have the opportunity to experience the tertiary clinical service at neighbouring Kellgren Centre for Rheumatology at Manchester Royal Infirmary. Extensive support will be given in laboratory technique, data cleaning, adverse event coding, statistical analysis and a clear route through to translation via BILAG group.
Funding Notes
Candidates will hold a medical degree and show evidence of interest in musculoskeletal research. Ideally candidates would hold a postgraduate degree, such as Masters, have a track record in clinical research and demonstrate a commitment to an academic career.
This is a Clinical Research Fellowship PhD project. Applicants must be from the UK/EU and funding covers fees/salary (an appropriate amount in line with the applicant's current salary and grade) for three years.
Applicants may contact the Primary Supervisor directly with any questions. Online applications must be submitted, select 'Manchester BRC' as the programme - for more information please visit https://www.bmh.manchester.ac.uk/study/research/funded-programmes/mbrc-studentships/
This is a Clinical Research Fellowship PhD project. Applicants must be from the UK/EU and funding covers fees/salary (an appropriate amount in line with the applicant's current salary and grade) for three years.
Applicants may contact the Primary Supervisor directly with any questions. Online applications must be submitted, select 'Manchester BRC' as the programme - for more information please visit https://www.bmh.manchester.ac.uk/study/research/funded-programmes/mbrc-studentships/
References
1. Yusof MY et al. Predicting and managing primary and secondary non-response to rituximab using B-cell biomarkers in systemic lupus erythematosus. Ann Rheum Dis Nov;76(11):1829-1836.
2. McCarthy E et al. Short-term efficacy and safety of rituximab therapy in refractory systemic lupus erythematosus: results from the British Isles Lupus Assessment Group Biologics Register
3. Mendoza-Pinto C, et al. Can We Identify Who Gets Benefit or Harm from Mycophenolate Mofetil in Systemic Lupus Erythematosus? A Systematic Review. Semin Arthritis Rheum. 2017 Feb
4. Pirone C et al. Predictive and prognostic factors influencing outcomes of rituximab therapy in systemic lupus erythematosus (SLE): A systematic review. Semin Arthritis Rheum. 2017 Dec;47(3):384-396.
5. Cobo-Ibáñez T et al. Efficacy and safety of rituximab in the treatment of non-renal systemic lupus erythematosus: a systematic review. Semin Arthritis Rheum. 2014 Oct;44(2):175-85
2. McCarthy E et al. Short-term efficacy and safety of rituximab therapy in refractory systemic lupus erythematosus: results from the British Isles Lupus Assessment Group Biologics Register
3. Mendoza-Pinto C, et al. Can We Identify Who Gets Benefit or Harm from Mycophenolate Mofetil in Systemic Lupus Erythematosus? A Systematic Review. Semin Arthritis Rheum. 2017 Feb
4. Pirone C et al. Predictive and prognostic factors influencing outcomes of rituximab therapy in systemic lupus erythematosus (SLE): A systematic review. Semin Arthritis Rheum. 2017 Dec;47(3):384-396.
5. Cobo-Ibáñez T et al. Efficacy and safety of rituximab in the treatment of non-renal systemic lupus erythematosus: a systematic review. Semin Arthritis Rheum. 2014 Oct;44(2):175-85
