Lympho-myeloid pathotype linked to more aggressive disease in RA
medwireNews: Having a lympho-myeloid pathotype at onset of rheumatoid arthritis (RA) is associated with an increased subsequent need for biologic therapy, irrespective of clinical classification, study findings indicate.
Costantino Pitzalis (William Harvey Research Institute, London, UK) and co-investigators believe their study “provides support to the notion that biological therapies should be started early in patients with poor prognosis.”
The analysis of 200 treatment-naïve patients with early arthritis found that 64.0% fulfilled the RA1987 ACR criteria, 12.5% fulfilled the RA2010 ACR/EULAR criteria, and the remaining 23.5% had undifferentiated arthritis (UA).
Immunohistochemical analysis of synovial tissue from 116 of the patients showed that 37.3%, 34.3%, and 28.3% had lympho-myeloid, diffuse-myeloid, and pauci-immune pathobiology, respectively, and the proportions did not differ significantly according to disease duration at baseline.
Patients in the lympho-myeloid group had significantly higher mean baseline DAS28 scores than those in the diffuse-myeloid or pauci-immune groups (5.82 vs 4.93 and 4.86, respectively) and, at 12 months, were significantly more likely to be receiving biologic therapy, at 57% versus 21% and 21%, respectively.
Writing in the Annals of the Rheumatic Diseases, Pitzalis and co-authors say this finding reinforces “recently published data that indicate that these patients are affected by highly aggressive disease and worse radiographic outcome.”
They add that the fact that the results were independent of the time from diagnosis suggests “the so-called ‘window of opportunity’ is wider than 6 months and early stratification of biological therapies according to poor prognostic synovial pathobiological subtypes at disease onset may improve the outcome of these patients.”
The researchers also looked at gene expression profiles among the patients and found 119 genes that were differentially expressed between the patients who did and did not require biologic therapy. These included genes involved in B- and T-cell regulation, matrix metallopeptidase activation, cytokine-mediated cellular activation, and osteoclastogenesis inhibition.
Adding these genes to a prediction model that incorporated DAS28, pathotype, C-reactive protein, and total joint count improved its ability to predict the need for biologic therapy from 79% to approximately 90%.
Pitzalis and team say: “The capacity to refine early clinical classification criteria through the application of synovial pathobiological markers and the ability to identify patients who subsequently require biological therapy at disease onset offer the opportunity to stratify therapeutic intervention to the patients most in need.”
They add: “This present study adds weight to the need to change current therapeutic algorithms and start biological therapies at disease onset in patients with poor prognosis.
“This is likely to have a major impact on disease control/remission and long-term disability, as notionally supported by numerous early intervention studies using biological therapies.”
By Laura Cowen
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