Session Type: Abstract Submissions (ACR)
Background/Purpose: The Rituximab in Myositis (RIM) Study provides a unique resource for biomarker investigation of homogeneously treated refractory adult and juvenile myositis patients. Building on prior cross-sectional findings, we examined the longitudinal utility of Type 1 interferon (IFN)-driven chemokines as clinical biomarkers of disease activity in myositis patients treated with B cell depletion.
Methods: All 200 enrolled refractory myositis patients (failed steroids and ≥1 other immunosuppressive agent) received 1 gram of rituximab on 2 consecutive weeks – weeks 0/1 (Early) or weeks 8/9 (Late). Using serum samples collected at weeks 0 and 16, multiplexed sandwich immunoassays (Meso Scale Discovery) quantified IFN-regulated chemokines and other pro-inflammatory cytokines. An IFN chemokine score combining IFN-inducible T-cell chemoattractant (I-TAC), IFN-inducible 10-kd protein (IP-10), and monocyte chemotactic protein 1 (MCP-1) was computed. Data collected at each visit included: muscle enzymes, physician global, muscle and extramuscular visual analog scale (VAS) scores (0-10 cm) and Myositis Disease Activity Assessment Tool variables (i.e., VAS score for organ involvement). Pulmonary involvement was defined as VAS>1 cm and included active interstitial lung disease (ILD) and respiratory muscle weakness (i.e., dysphonia and dyspnea). Changes in IFN chemokine and VAS scores were calculated as week 16 – week 0, and correlations were assessed using Spearman methods.
Results: In 181 patients (87 Early, 94 Late) with available serum samples, changes in IFN chemokine score correlated with changes in physician global (r=0.19 p=0.017), muscle (r=0.19 p=0.019) and extramuscular VAS (r=0.24 p=0.002). These associations persisted after adjusting for muscle enzymes (global r=0.15 p=0.056; muscle r=0.16 p=0.046 and extramuscular r=0.25 p=0.002), suggesting that the IFN chemokine score is complementary to muscle enzymes. The IFN chemokine score at week 0 correlated with change in extramuscular VAS (r=-0.18 p=0.027), but not with change in global or muscle VAS (r<0.1).
In patients with pulmonary involvement (n=70), IFN chemokine score at week 0 was more strongly correlated with changes in disease activity (global r=-0.37 p=0.004; muscle r=-0.36 p=0.005; extramuscular r=-0.41 p=0.001) than in patients without pulmonary involvement (n=111; r=0 to 0.14). The change in IFN chemokine score was also more strongly correlated with the change in disease activity by VAS among patients with pulmonary involvement (global r=0.27 p=0.04; muscle r=0.45 p<0.001; extramuscular r=0.41 p=0.001) compared to patients without pulmonary involvement (r=0.06 to 0.15). Results for patients with active ILD (n=32) were similar to those for non-parenchymal pulmonary involvement.
Conclusion: Changes in IFN chemokine score correlated with changes in disease activity, particularly among myositis patients with pulmonary involvement (with or without active ILD). The IFN chemokine score may be a useful clinical biomarker for patients with myositis, especially in patients with lung involvement. In addition, these chemokines may provide useful insights into the pathogenesis of myositis or specific manifestations.
C. S. Crowson,
A. M. Reed,
NIH, NIAMS, State of MN Partnership,
A. B. Green,
C. Lopez de Padilla,
D. P. Ascherman,
M. C. Levesque,
Genentech and Biogen IDEC Inc.,
C. V. Oddis,
« Back to 2012 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/interferon-driven-chemokines-are-associated-with-changes-in-disease-activity-among-rituximab-treated-refractory-myositis-patients-with-pulmonary-involvement-the-rim-study/