Search

Objective. To study the effect of various basic and genetic engineering biological therapies (infliximab, rituximab, tocilizumab) used as first, second- and third-line drugs in combination with methotrexate on clinical course, quality of life (QOL), and the evolution of articular erosions and synovitis in patients with rheumatoid arthritis (RA) during 12 months of follow-up.Material and methods. This paper is an open observational study of the efficacy and safety of various basic and genetic engineering biological therapy agents (bDMARD) in patients with early active RA who are in the Mechnikov North-West State Medical University registry. Included are 151 patients with early RA (eRA), the average age is 58.2 ± 5.5 years, the disease duration is 6.5 ± 0.3 months, DAS 28-CRP – 4.48 ± 0.87. At the first stage, basic therapy was administered to patients with eRA by random sampling: sulfasalazine (CC) 2 g per day (group I – 55 patients), methotrexate (MT) – 20 mg per week (group II – 55 patients), or leflunomide (LF) 20 mg per day (group III – 41 patients). The follow-up was 12 months. At the second stage, 101 patients with persisting moderate (DAS 28: 3.2–5.1) and high levels of RA activity (DAS 28 > 5.1) despite ongoing therapy with DMARDs were assigned MT at a dose of 25 mg per week (subgroup 1–25 patients), or MT – 20 mg per week in combination with infliximab (INF) – 3 mg/kg (subgroup of 2–25 patients), or – MT 20 mg per week and rituximab (RM) – two infusions of 1000 mg at the week 0 and 2 and then at the week 52nd and 54th with a duration of observation of 12 months. In the third stage, 20 patients (16 women and 4 men aged 28 to 67 years) with a high disease activity DAS 28-CRP despite previous therapy with MT and INF or RM were transferred to therapy with an IL6 – tocilizumab receptor blocker as a second-line or third-line drug. The duration of observation ranged from 6 months to five years.Results. By 12 months of treating DMARDs, clinical remission was achieved more often in the MT group than in the LF group (43.2 and 32.4 %) (p < 0.05), and was accompanied by a decrease in the expression of markers of early activation of T-lymphocytes, IL-1β, IL-2 and IL-4. In the SS group, clinical remission was not observed, while there was a significant increase in the median of the total Sharpe score and erosion score relative to the baseline. The prescription of INF or PM as the first bDMARD after 12 months led to a significant increase in the physical and psychological components of the patients' QL and positive dynamics of the HAQ index compared to baseline values. The use of tocilizumab as a second-line and third-line drug in patients with active RA and the ineffectiveness of previous therapy for DMARD and bDMARD contributed to a significant decrease in DAS 28-CRP by as early as 24 weeks of follow-up. Cases of serious adverse reactions (AE) are not marked.Conclusions. There were no statistically significant differences in the dynamics of CRP, ESR, circulating immune complex and X-ray progression indicators between the groups of patients who received biological therapy of INF and RM, which confirms the possibility of ‘switching’ therapy from the first bDMARD to the drugs of subsequent lines with an increase in the clinical activity of RA. Tocilizumab can be a second- and third-line drug with an ‘escape’ effect from other bDMARDs.

The article reviews the clinical symptoms, main complications in patients with ANCA-associated systemic vasculitis (granulomatous with polyangiitis, microscopic polyangiitis, eosinophilic granulomatous with polyangiitis) and polyarteritis nodosa during the first three years of the disease. We evaluated the relationship between complications and long-term glucocorticosteroid therapy. Patients with granulomatosis had the most unfavourable course of the disease with a high risk of complications. A high incidence of ischemic strokes and chronic kidney disease in patients with microscopic polyangiitis has been identified. We also analyzed cases of lethal outcomes in patients with primary systemic vasculitis.