Impact of tocilizumab therapy on fatigue in patients with rheumatoid arthritis
Objective: to study the impact of tocilizumab (TCZ) therapy on fatigue symptom in patients with rheumatoid arthritis (RA). Subjects and methods. The study covered 43 RA patients receiving therapy with TCZ in a dose of 8 mg/kg once four times for 24 weeks. Most patients were females, they were aged 25 to 69 years with a one-to-10-year history of the disease; 86% of the patients were rheumatoid factor-positive; 84% were anti-cyclic citrullinated peptide-positive; 42 and 49% had X-ray Stage II or III, respectively; 81% had Functional Class II; and 77% had high DAS 28 scores. Twelve (28%) of the 43 patients included into the study were found to have anemia with lower hemoglobin levels (< 110 g/l). Prior to TCZ therapy, all the patients had received for at least 6 months disease-modifying antirheumatic drugs, mainly methotrexate, in an average dose of 15.0+2.7 mg; 59.5% of the patients had taken glucocorticoids in the average dose of 7.5+2.22 mg/day, calculated with reference to prednisolone. Fatigue was rated in centimeters, by applying the visual analog scale of the RAPID-3 questionnaire. Results. The fatigue symptom was found to have the most pronounced correlations with depression (R = 0.49), pain (R = 0.48), DAS 28 scores (R = 0.47), erythrocyte sedimentation rate (ESR) (R = 0.49), and total disease activity scores (R = 0.55). The relationships to the number of tender and swollen joints, hemoglobin and interleukin-6 (IL-6) levels turned out to be less significant. The level of fatigue significantly decreased from 5.3 to 4.5 cm after the first TCZ infusion just at 4 weeks of a follow-up. Later on, it continued to fall and reached 2.5 cm at 24 weeks. During the therapy, fatigue generally diminished by 52%. There were significant reductions in the scores of DAS 28 (from 6.3 to 2.23), SDAI (from 41.75 to 4.55), CDAI (from 44.03 to 4.07), RAPID-3 (p < 0.01), pain (from 6.6 to 1.2 cm), ESR, C-reactive protein, IL-6, and a considerable functional improvement in HAQ (from 1.75 to 0.5 scores). It should be noted that all the indicators rapidly improved just after the first infusion of the drug. Following 8 weeks of TCZ therapy, low disease activity was observed in 24.4% of the patients; 26.8% achieved clinical and laboratory remissions. At 24 weeks, 11.9% had low DAS 28 scores and 71.4% had a remission.