P240 Predictors and prognostic factors influencing outcomes of anti-CD20 monoclonal antibodies in systemic lupus erythematosus: a systematic review update
Authors: Rodziewicz Mia , Dyball Sarah , Mendoza-Pinto Claudia , Munguia-Realpozo Pamela , Bruce Ian N , Parker Ben 
Published: April 2022

Abstract

Background/Aims
Anti-CD20 monoclonal antibodies (MAb) are used to deplete B cells in autoimmune and haematological disease. Rituximab (RTX) failed to meet its primary endpoint in two Phase III trials for systemic lupus erythematosus (SLE) but is commonly used for the treatment of patients with severe or refractory disease. outcomes including clinical response and adverse effects are highly variable. Alternative anti-CD20 MAbs such as Ofatumumab, have been suggested as a potentially effective alternative treatment for those patients who fail treatment with RTX. We aimed to provide an update of a systematic review of predictive and prognostic factors of anti-CD20 MAb treatment in SLE patients.

Methods
A systematic literature search was undertaken and included adult and paediatric randomised controlled trials (RCTs) and cohort studies. Articles included in the previous systematic review were excluded. Methodological quality was assessed for RCTs using the Cochrane Collaboration Risk of Bias (RoB2) tool for RCTs and the Quality In Prognosis Studies Tool (QUIPS) for cohort studies. The quality of evidence (QoE) was assessed as high, moderate, low or very low using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach for RCTs and the 2013 adaptation for prognostic factor research. The quality of subgroup analysis for predictors of differential treatment response was also evaluated. A narrative synthesis of the evidence from included studies was undertaken in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Results
Sixteen studies from an initial 849 results were included. There were two post-hoc analyses of RCTs of RTX, one RCT of ocrelizumab in lupus nephritis and 13 cohort studies examining RTX treatment. Outcomes assessed included global clinical, cutaneous, haematological and renal response, treatment failure, relapse and adverse effects. The overall QoE was assessed as low and very-low for all studies and was limited by significant heterogeneity of inclusion criteria, assessment tools, outcomes assessed and definitions of response and failure. Studies also often included small numbers of participants and failed to account for confounders and multiple subgroup analyses of differing outcomes. Novel biomarkers, such as S100 proteins, anti-vimentin and anti-drug antibodies showed some evidence of prognostic value but QoE was limited due to moderate to high risk of bias, early phase of investigation and imprecision of results.

Conclusion
Since 2015, there has been little progress in the identification and confirmation of prognostic or predictive factors to guide outcome in lupus patients treated with anti-CD20 therapy. Further work is required to support those factors which appear to demonstrate prognostic potential. PROSPERO registration number: CRD42020220339

Disclosure
M. Rodziewicz: Grants/research support; M.R. is supported by the NW England MRC Fellowship in Clinical Pharmacology and Therapeutics, which is funded by the MRC, Riche, Eli Lily UCB, Novartis and the Universities of Manchester and Liverpool. S. Dyball: Grants/research support; S.D. is supported by the NW England MRC Fellowship in Clinical Pharmacology and Therapeutics, which is funded by the MRC, Roche, Eli Lily UCB, Novartis and the Universities of Manchester and Liverpool. C. Mendoza-Pinto: None. P. Munguia-Realpozo: None. I.N. Bruce: Grants/research support; I.N.B. has received grants from GlaxoSmithKline and Sanofi Genzyme. Other; I.N.B. has received consultancy and speaker fees to his institution from GlaxoSmithKline, UCB, BMS, Eli Lily, Aurinia, AstraZeneca and Merck Serono. B. Parker: None.