Background/Purpose: Tocilizumab, an interleukin-6 (IL-6) receptor antagonist, is an effective drug for the treatment of rheumatoid arthritis (RA). During administration of tocilizumab, previous studies have shown that the levels of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), classic acute phase reactants, might not be elevated even in RA patients with high inflammatory activity due to infection. Therefore, we evaluated whether neutrophil–lymphocyte ratio (NLR), which has been recently introduced as a useful parameter for monitoring the disease activity in systemic inflammatory diseases, reflect treatment response to tocilizumab therapy better than ESR and CRP in patients with RA.

Methods: A total of 72 RA patients treated with tocilizumab in a single tertiary referral hospital from Jan 2013 to Dec 2014 were initially included in our study. We excluded 30 patients due to infection (n=9), administration less than six months (n=8), adverse event (n=6), violation of interval (n=5), pregnancy (n=1), and combined malignancy (n=1). Out of the remaining 42 patients, 14 experienced flare-up during tocilizumab therapy. Flare-up was defined as events that needed either dose escalation of steroid, intra-articular steroid injection or switch tocilizumab to another biologic agent. The data were retrospectively reviewed with the electronic medical records. We compared levels of inflammatory markers including leukocyte count, ESR, CRP and NLR at flare-up and stable state before flare-up. Moreover, 28 patients with stable RA after tocilizumab administration were also evaluated. The levels of inflammatory markers were compared at three and six months after initiation of tocilizumab.

Results: In the group of patients who experienced flare-up during tocilizumab treatment, the levels of CRP were not significantly different between those measured at stable state and flare-up (0.32 ± 0.45 vs 0.73 ± 1.03 mg/dL, p=0.110). The levels of ESR and the values of NLR were significantly different between those measured at stable state and flare-up (14.9 ± 15.8 vs 24.3 ± 23.3 mm/hr, p=0.041 and 1.98 ±1.01 vs 4.05 ± 3.42, p=0.002). The levels of ESR and CRP measured at flare-up ranged within the normal limit in eight and nine patients each, and four and three patients each had decreased levels of ESR and CRP at flare-up compared with those at stable state. However, the values of NLR in all patients except one patient increased significantly at flare-up compared to stable state, and the percentage of increment ranged from -13 to 437%(105 ± 42). In the group of patients who were stable during tocilizumab treatment, the levels of NLR did not change between those measured at three and six months after initiation of tocilizumab (1.47 ± 0.70 vs 1.30 ± 0.69, p=0.233).

Conclusion: The levels of CRP did not reflect treatment response to tocilizumab administration in RA patients, whereas the values of NLR were significantly increased in the flare group. The values of NLR were more associated with treatment response to tocilizumab than the levels of ESR. Thus, our present findings suggest that NLR is more valuable for evaluating the disease activity in patients with RA during tocilizumab therapy.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/neurophil-to-lymphocyte-ratio-is-a-reliable-marker-of-treatment-response-in-rheumatoid-arthritis-patients-during-tocilizumab-therapy/