Background/Purpose:

Serum cytokines play an important role in the pathogenesis of myositis by initiating and perpetuating various cellular and humoral autoimmune processes. The aim of this study was to measure interferon (IFN)-inducible chemokines, Th1, Th2, Th17, innate, and regulatory cytokines in patients with refractory idiopathic inflammatory myositis (IIM) to identify a biomarker signature to predict responsiveness to rituximab.

Methods:

In a randomized, placebo-phase trial (Rituximab in Myositis (RIM)), 200 refractory IIM subjects received 1 gm of rituximab on 2 consecutive weeks – weeks 0/1 (Early) or weeks 8/9 (Late). Serum samples were collected at baseline, 8, and 16 weeks following treatment.  Multiplexed sandwich immunoassays (Meso Scale Discovery) were used to measure IFN-regulated chemokines and other pro- and anti-inflammatory cytokines specific to differentiation of specific T cell and innate pathways. Cytokine scores were computed for Th1 (IFNy, TNFα, and IL2), Th2 (IL4, IL5, IL10, IL12, and 1L 13), Th17 (IL6, IL17, IL1β), innate (IFNα, MCP-1, MCP-2, MIG, MIP-1β, IP-10, I-TAC, IL18), IFN-regulated chemokine (I-TAC, IP-10, MCP-1), and regulatory(IL10, TNFα) factors.  IMACS core set myositis disease activity measures (physician global, patient global, MMT, HAQ, muscle enzyme, and extramuscular visual analog scale (VAS) scores (0-100 mm) and Myositis Disease Activity global VAS were collected at each visit. Changes in IFN chemokine and cytokines and VAS scores between time points were calculated, and were correlated using Spearman methods.

Results:

We analyzed data available for 177 myositis subjects (mean age (SD)/disease duration (SD) 37(19)/5(7) years, 73% female, 70% Caucasian.  The mean (SD) values for muscle disease activity and physician global disease activity VAS scores were 46(22) and 49(19) cm, respectively.  Increased levels of Th2, Th17 and innate cytokines were observed 16 weeks after the start of treatment (p = 0.05, p = 0.02, p < 0.001, respectively), while the levels of regulatory cytokines were reduced (p < 0.001).  IFNCK, Th1, Th2, Th17, innate, and regulatory cytokine scores at baseline were positively correlated with physician global VAS at the start of treatment (r=0.20 [P=.01],  r=0.29 [P<.001], r=0.16 [P=.03], r=0.18 [P=.02], (r=0.19 [P=.01], and (r=0.19 [P=.01], respectively); while Th1, Th2, and Th17 cytokine scores correlated positively with muscle disease activity VAS at the start of treatment (r=0.22 [P=.003], r=0.17 [P=0.02], (r=0.22 [P=.003], respectively).  Higher baseline IFNCK and innate cytokine scores were predictive of better response in physician global VAS at 16 weeks after treatment (r= -0.167 [P=.03], (r= -0.15 [P=.05], respectively). In addition, baseline IFNCK, innate and regulatory cytokine scores correlated with muscle improvement on the MDAAT at 8 weeks ([r= -0.19, P= .01], [r= -0.20, P=.01], [r= -0.21, P=.005] respectively) while baseline IFNCK and innate cytokine scores correlated with muscle improvement at 16 weeks ([r= -0.17, P= .03], [r= -0.16, P= .04], respectively).

Conclusion:

IFNCK and innate cytokine scores before treatment may help to identify rituximab responsiveness in refractory myositis patients.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/interferon-regulated-chemokine-and-innate-cytokine-scores-identify-refractory-myositis-patients-that-respond-better-to-rtuximab-therapy/