Dokl Biochem Biophys. 2026 Mar 30. doi: 10.1134/S1607672925700231. Online ahead of print.
ABSTRACT
Interleukin (IL)-6 plays an important role in the pathogenesis of comorbid rheumatoid arthritis (RA) depression. IL-6 inhibitors used to treat patients with RA may also have an antidepressant effect. THE OBJECTIVE-: of this study is to evaluate the effectiveness of 24-week IL-6 inhibitor therapy with olokizumab (OKZ) in combination with or without psychopharmacotherapy (PPT) in patients with moderate to high RA activity.
MATERIALS AND METHODS: -A total of 125 patients with RA were included, 102 (81.6%) of them were women. The average age of the patients was 48.5 ± 12.6 years; the majority of the patients (86.4%) had high RA activity and had shown ineffectiveness with stable 12-week therapy using conventional synthetic disease modifying antirheumatic drugs (csDMARDs). Additionally, 34 (27.2%) patients had shown inefficiency with one or more biological DMARDs. According to the International Classification of Diseases, 10th revision (ICD-10), a psychiatrist diagnosed varying severity of depression (chronic or recurrent) in all patients during a semi-structured interview. At week 0, all patients were randomized using sequential numbers in a 2:2:1 ratio into one of three groups: in group 1, patients received csDMARDs + OKZ 64 mg subcutaneously once every 4 weeks (q4w) (n = 49); in group 2, patients received csDMARDs + OKZ 64 mg subcutaneously q4w along with PPT (n = 51); in group 3, patients received csDMARDs + PPT (n = 25). The study duration was 24 weeks. The severity of depression was assessed using the PHQ-9 (Patient Health Questionnaire 9) and MADRS (Montgomery-Asberg Depression Rating Scale) scales, and anxiety was assessed using the HAM-A (Hamilton Anxiety Rating Scale) scale. Projective experimental psychological techniques were also used.
RESULTS: -After 12 and 24 weeks of therapy, a significant decrease in the severity of depression and anxiety was observed in all patients’ groups. However, the differences between the final and initial values of the scales filled in by a psychiatrist were statistically significantly greater (p < 0.001) in the groups of patients receiving PPT: in group 2 (ΔMADRS24-0 = -20.2 ± 6.57; ΔHAM-A24-0 = -13.2 ± 5.68) and group 3 (ΔMADRS24-0 = -17.8 ± 4.73; ΔHAM-A24-0 = -13.4 ± 4.41), compared with the group 1 (ΔMADRS24-0 = -5.42 ± 7.14; ΔHAM-A24-0 = -4.58 ± 6.80). There were no significant differences between the groups according to the PHQ-9 depression questionnaire (in group 1, ΔPHQ-924-0 = -4.89 ± 4.87; in group 2, ΔPHQ-924-0 = -6.73 ± 4.97; in group 3, ΔPHQ-924-0 = -7.26 ± 5.58, respectively), despite a greater decrease in the severity of depression observed in the groups with PPT. According to a semi-structured interview with a psychiatrist and in accordance with the criteria of ICD-10 the proportion of patients without depression 24 weeks after the start of therapy was significantly higher in the groups receiving PPT: 84.3% in group 2, 100% in group 3, and 16.3% in group 1.
CONCLUSIONS: -In patients with moderate/high RA activity and comorbid depression, OKZ without PPT can lead to a decrease in the severity of depression or, less often, to a complete regression of depressive symptoms, mainly in patients with minor depression. OKZ therapy without PPT also reduces the severity of anxiety, but does not eliminate it completely. The combination of OKZ and PPT is optimal for achieving complete regression of depression and anxiety in this category of RA patients.
PMID:41912840 | DOI:10.1134/S1607672925700231
