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Predictive and prognostic factors influencing outcomes of rituximab therapy in systemic lupus erythematosus (SLE): A systematic review.

ABSTRACT: BACKGROUND:The clinical outcomes following rituximab (RTX) treatment in patients with systemic lupus erythematosus (SLE) is highly variable. We aimed to identify predictive and prognostic factors associated with RTX therapy outcomes in patients with SLE. METHODS:Studies in adults and paediatric patients with SLE were included. We included randomized clinical trials (RCTs) for predictors of differential treatment effect and cohort studies for potential prognostic factors in patients treated with RTX (global clinical, cutaneous and renal either response or relapse, and side effects). Methodological quality was assessed using Cochrane Collaboration Risk of Bias tool and the Quality In Prognosis Studies Tool (QUIPS) for RCTs and cohort studies, respectively. The quality of subgroup analyses testing predictors of differential treatment response was also evaluated. A best evidence synthesis was performed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. RESULTS:Sixteen articles were included (3 from 2 RCTs and 13 from 6 cohort studies). The overall quality of evidence (QoE) was low to very low (GRADE framework). QoE for predictive factors based on RCTs analysing sociodemographic variables, was rated very low due to the lack of interaction tests, limited power of subgroup analyses, study limitations, and imprecisions. Disease-related factors including clinical phenotype and severity, baseline anti-ENA antibodies and anti-Ro antibodies, interleukin (IL) 2/21 single nucleotide polymorphism (SNP), as well as post-RTX complete B-cell depletion and earlier B-cell repopulation showed some evidence for prognostic value, but were rated low to very low QoE because of early phase of investigation (exploratory analysis), insufficient adjustment for confounding in most studies, high risk of bias, inconsistency, and imprecisions. CONCLUSIONS:To date, studies addressing prognostic factors are hypothesis generating and cannot be used to make any specific recommendations for routine clinical practice. A number of potential predictors/prognostic factors were identified, which require to be validated as being specific for response to RTX therapy and to enable more personalised use of this agent.

SUBMITTER: Pirone C

PROVIDER: S-EPMC5695978 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Predictive and prognostic factors influencing outcomes of rituximab therapy in systemic lupus erythematosus (SLE): A systematic review.

Pirone Carmelo C Mendoza-Pinto Claudia C van der Windt Daniëlle A DA Parker Ben B O Sullivan Miriam M Bruce Ian N IN

Seminars in arthritis and rheumatism 20170505 3

<h4>Background</h4>The clinical outcomes following rituximab (RTX) treatment in patients with systemic lupus erythematosus (SLE) is highly variable. We aimed to identify predictive and prognostic factors associated with RTX therapy outcomes in patients with SLE.<h4>Methods</h4>Studies in adults and paediatric patients with SLE were included. We included randomized clinical trials (RCTs) for predictors of differential treatment effect and cohort studies for potential prognostic factors in patient ...[more]

PMID: 28602359

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Project description:ObjectiveTo identify interactions between genetic factors and current or recent smoking in relation to risk of developing systemic lupus erythematosus (SLE).MethodsFor the study, 673 patients with SLE (diagnosed according to the American College of Rheumatology 1997 updated classification criteria) were matched by age, sex, and race (first 3 genetic principal components) to 3,272 control subjects without a history of connective tissue disease. Smoking status was classified as current smoking/having recently quit smoking within 4 years before diagnosis (or matched index date for controls) versus distant past/never smoking. In total, 86 single-nucleotide polymorphisms and 10 classic HLA alleles previously associated with SLE were included in a weighted genetic risk score (wGRS), with scores dichotomized as either low or high based on the median value in control subjects (low wGRS being defined as less than or equal to the control median; high wGRS being defined as greater than the control median). Conditional logistic regression models were used to estimate both the risk of SLE and risk of anti-double-stranded DNA autoantibody-positive (dsDNA+) SLE. Additive interactions were assessed using the attributable proportion (AP) due to interaction, and multiplicative interactions were assessed using a chi-square test (with 1 degree of freedom) for the wGRS and for individual risk alleles. Separate repeated analyses were carried out among subjects of European ancestry only.ResultsThe mean ± SD age of the SLE patients at the time of diagnosis was 36.4 ± 15.3 years. Among the 673 SLE patients included, 92.3% were female and 59.3% were dsDNA+. Ethnic distributions were as follows: 75.6% of European ancestry, 4.5% of Asian ancestry, 11.7% of African ancestry, and 8.2% classified as other ancestry. A high wGRS (odds ratio [OR] 2.0, P = 1.0 × 10-51 versus low wGRS) and a status of current/recent smoking (OR 1.5, P = 0.0003 versus distant past/never smoking) were strongly associated with SLE risk, with significant additive interaction (AP 0.33, P = 0.0012), and associations with the risk of anti-dsDNA+ SLE were even stronger. No significant multiplicative interactions with the total wGRS (P = 0.58) or with the HLA-only wGRS (P = 0.06) were found. Findings were similar in analyses restricted to only subjects of European ancestry.ConclusionThe strong additive interaction between an updated SLE genetic risk score and current/recent smoking suggests that smoking may influence specific genes in the pathogenesis of SLE.

Dataset Information

Predictive and prognostic factors influencing outcomes of rituximab therapy in systemic lupus erythematosus (SLE): A systematic review.

Publications

Predictive and prognostic factors influencing outcomes of rituximab therapy in systemic lupus erythematosus (SLE): A systematic review.

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