Dynamics of inflammatory markers and interleukin 6 levels during olokizumab therapy: Results of a single-center randomized controlled trial

The aim – to evaluate the effect of olokizumab (OKZ) on acute-phase reactants, interleukin (IL) 6, and its soluble receptor (sIL-6R) levels in patients with rheumatoid arthritis (RA) and comorbid depression.

Material and methods. A total of 125 patients with RA and comorbid depression were included, including 102 (81.6%) women, with a mean age of 48.5±12.6 years. The majority (86.4%) had high RA activity and had failed stable 12-week therapy with synthetic disease-modifying antirheumatic drugs (DMARDs). Thirty-four (27.2%) patients had failed one or more biological agents. At week 0, all patients were randomized using the sequential numbers method in a 2:2:1 ratio to one of three groups: Group 1 received treatment with sDMARDs + OKZ 64 mg subcutaneously once every 4 weeks (n=49); group 2 – sDMARDs + OKZ 64 mg subcutaneously + psychopharmacotherapy (PPT) (n=51); group 3 – sDMARDs + PFT (n=25). The study duration was 24 weeks. Serum IL-6 concentrations were determined using xMAP multiplex technology on a Bio-Plex Array System analyzer (Bio-Rad, USA) and immunochemiluminescence assay (ICL) on a Cobas e411 analyzer (Roche, Switzerland).

Results. The use of OKZ was accompanied by a significant decrease in the level of C-reactive protein (CRP) and calprotectin (CP) in the group as a whole; normalization of the CRP level was noted 4 weeks after the start of therapy (p<0.05). When comparing the groups of patients who achieved (n=50) and did not achieve remission (n=50) according to the EULAR (European Alliance of Associations for Rheumatology) criteria (according to DAS28-CRP (Disease Activity Score 28 with CRP determination)) by 24 weeks of OKZ therapy, significant differences were noted in the concentration of CP (respectively, 1.54 [1.2; 2.56] versus 2.42 [1.5; 4.54] μg/ml; p=0.022) in contrast to CRP (0.45 [0.2; 0.7] versus 0.6 [0.2; 0.9] mg/ml). There was a significant decrease in the concentration of IL-6 in the group as a whole by 5.5 times after 12 weeks and by 3.5 times after 24 weeks of therapy. The level of sIL-6R decreased in the group as a whole and among patients with a good response to therapy (p<0.05).

Conclusion. Thus, the use of OKZ is accompanied by a decrease in the levels of acute-phase reactants, CP, IL-6, and sIL-6R. CP can be considered a more sensitive marker for assessing inflammation during OKZ therapy compared to CRP.

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