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.

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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/