Background/Purpose: Rheumatologists have been encouraged to achieve low disease activity state when treating rheumatoid arthritis (RA).  If it cannot be achieved with initial therapy, experts recommend changing to a different mechanism of action.  There is no established means of selecting among the mechanisms of action. 

RA is a heterogeneous disease with variations in presentation, extra-articular features, and response to treatment. No single biomarker has been identified to predict response to treatment. Many cytokines have been identified in RA.  12 have become available in one test (MBDA).  This study attempted to determine if the patterns of cytokine elevations could be used for treatment selection.

Methods: A literature search was performed, identifying clinical trials on RA which measured responses to the cytokines included in the MBDA: VCAM-1, VEGF-A, IL-G, TNF, MMP-1, MMP-3, YKL-40, Leptin, Resistin, SSA, and CRP. The trials included hydroxychloroquine (HCQ), sulfasalazine (SSZ), methotrexate (MTX), leflunomide (LEF), abatacept (ABA), tocilizumab (TCZ), rituximab (RTX) and tofacitinib (TOFA). A table(Table1) was constructed of cytokines versus treatment. Patients seen in the practice with RA were given the MBDA, and treatment was selected based on the agents with efficacy on highest number of cytokines elevated or past the 40th percentile reported on the MBDA, excluding EGF (elevated in remission) and leptin, which is affected by body composition, whenever pre-existing conditions, insurance coverage, and patient preference allowed. 263 patients were tested, 2 to 4 times over a 14 month period during routine visits.

Example: 83 year old patient with 6 year history RA: rheumatoid factor 169.6, CCP > 250, Larsen II radiographic changes. Past treatment: prednisone and MTX.  MBDA score 09/06/2013: 69 high arthritis activity.  VCAM-1 97%, VEGF-A 52%, IL-6 >99%, MMP-1 80%, MMP-3 96%, YKL-40 66%, Resistin 54%, SSA 82%, CRP 98 % percentiles. TOFA prescribed.  Post treatment MBDA score 10/14/2016: 31 VCAM-1 67%, IL-6 30%, MMP-1 56%,MMP-3 29%, YLK-40 51%, Resistin 56%, SSA 19%, CRP 43%

Results: The MBDA scores in the physician’s practice were graphed against the national average MBDA scores in practices using conventional treat to target strategies (Figure 1).  Differences within the distribution of scores, and in the heights of the high, medium, and low MBDA scores can be observed between the two groups

Conclusion: This study is not meant to be a proof of concept achieved though a randomized controlled trial which demonstrated statistical significance.  The data from the clinical trials utilized in Table 1 and the practices contain heterogeneous populations of patients of unknown disease duration and dissimilar prior treatments.  This study is observational, without the structure of a clinical trial, generated during routine clinical practice, and could qualify as real world data.  Figure 1 may demonstrate an advantage to treatment selection based on the unique cytokine profiles of patient.  With the increasing numbers of mechanisms of action, rising costs of treatment, and the shift to value-based care, it may be of value to explore the utility of multiple biomarker arrays in achieving low disease activity states in a directed manner.

MBDA 531 2019

ACR Meeting Abstracts - https://acrabstracts.org/abstract/treat-to-target-by-specific-cytokine-interdiction-multiple-biomarker-disease-activity-test-deconstructed/