Thursday, 8 February 2018

Ken Baker - Thursday 1st March - 12.15pm - MED.L2.6

This should be interesting 😊

 

 

 

 

VIVA Seminar

 

Speaker: Ken Baker

Supervisors: Prof John Isaacs, Dr Arthur Pratt, Dr Ben Thompson

 

Predictors of Drug-Free Remission in Rheumatoid Arthritis

 

Background  Rheumatoid arthritis (RA) is a common autoimmune disease characterised by joint inflammation and systemic manifestations. Remission is achievable with disease- modifying anti-rheumatic drugs (DMARDs) prescribed in modern treat-to-target strategies, albeit with potential side effects, and inconvenient and expensive safety monitoring. Half of patients can maintain remission following DMARD cessation, though this cannot be reliably predicted. Clinicians and patients thus face a dilemma – when is it appropriate to stop DMARDs in RA remission?

Method Patients with established RA satisfying clinical and ultrasound remission criteria discontinued all DMARDs and were monitored for six months. The primary outcome was time-to-flare, defined as DAS28-CRP (disease activity score in 28 joints with C-reactive protein) ≥ 2.4. Baseline clinical and ultrasound measures, circulating cytokines, and peripheral CD4+ T cell gene expression were assessed for their ability to predict time-to- flare and flare/remission status by Cox regression and receiver-operating characteristic (ROC) analysis.

Results 23/44 (52%) eligible patients experienced an arthritis flare at a median (IQR) of 48 (31.5 – 86.5) days following DMARD cessation. A composite score incorporating five baseline variables (three genes, one cytokine and one clinical) differentiated future flare and drug- free remission with an area under the ROC curve of 0.96 (95% CI 0.92-1.00), sensitivity of

0.91 (0.78 – 1.00) and specificity of 0.95 (0.84 – 1.00). Longitudinal analysis identified increased concentrations of circulating pro-inflammatory cytokines, and upregulation of a

proliferative gene set by CD4+ T cells at the onset of flare.

Conclusions This study provides proof-of-concept evidence for the existence of biomarkers of drug-free remission in RA, and offers insights to the pathophysiology of arthritis flare. If validated, these biomarkers may help guide DMARD withdrawal, with consequent minimisation of medication side effects and healthcare costs.

 

Thursday 1st March, 12.15pm

Room L2.6, 2nd Floor William Leech Building

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