Features of iron metabolism disorders and the contribution of anemia to the development of fatigue in patients with active rheumatoid arthritis

The aim of the study – to analyze the relationship between iron metabolism disorders and the assessment of the main patient-reported outcomes (PROs) – fatigue, pain, functional limitations and quality of life, as well as the influence of anemia genesis on the effectiveness of therapy in patients with active rheumatoid arthritis (RA).

Materials and methods. The study included 108 patients with RA (DAS28 (Disease Activity Score 28) – 5.0±1.2) who were sequentially admitted for inpatient treatment at the V.A. Nasonova Research Institute of Rheumatology. The diagnosis of anemia was made according to World Health Organization criteria. The nature of iron metabolism disorders was verified by the level of serum hepcidin. Anemia of chronic inflammation (AI) was classified with an increase in hepcidin levels above reference values (>120 pg/ml), iron deficiency anemia (IDA) was diagnosed in patients with hepcidin levels below 40 pg/ml. All patients underwent PROs assessment using FACIT-F (Functional Assessment of Chronic Illness Therapy – Fatigue) – fatigue level, HAQ (Health Assessment Questionnaire) – functional impairment level, EQ-5D (EuroQol-5 Dimensions – patient’s quality of life.

Results. The incidence of anemia in patients with active RA was 46%. Among patients with anemia (n=47), isolated AI was diagnosed in 54% of cases (n=27). IDA was detected in 19 (37%) patients. In both types of iron metabolism disorders, the patients were comparable in age, duration of the disease, swollen joint count (SJC), patient’s pain level, HAQ and FACIT-F. Significant differences were obtained in terms of tender joint count (TJC; 6.0 [4.0; 9.0] and 9.0 [6.0; 14.0], DAS28 index (5.1±1.0 and 5.9±1.1), respectively. Fatigue correlated with HAQ (r=–0.49; p=0.04) and hemoglobin levels (r=0.49) in IDA (p=0,04). In AI, the fatigue level correlated with EQ-5D (r=–0.61; p=0.02) and with HAQ (r=0.71; p=0.00). Only in AI did fatigue correlate with IL-6 (gil-6=0.6; r=0.6; p=0.01). In patients with active RA and IDA, severe fatigue was almost twice as common as in AI (33% and 18%, respectively). There was no fatigue with AI in 37%, with IDA – in 28% of cases. Among patients with anemia who had a change of two classes of biological disease-modifying antirheumatic drugs(bDMARDs)/targeted synthetic DMARDs (tsDMARDs), the incidence of IDA was 75%.

Conclusions. Concomitant IDA makes a significant contribution to severe fatigue in active RA, which is poorly diagnosed by doctors due to the similarity of clinical manifestations with AI. It is patients with IDA who are three times more likely to have the change of two classes of bDMARDs/tsDMARDs compared with AI.

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