Abstract

Objective: to study the efficiency and tolerance of rituximab (RTM) treatment in patients with scleroderma systematica (SDS) with interstitial lung injury (ILI). Subjects and methods. The trial included 27 patients (26 women and 1 man) (mean age 45.7±13.0 years), with diffuse (n=13) and circumscribed (n = 14) forms and a disease duration of > 5 years in 63%. All the patients underwent chest computed tomography; examination of external respiratory function, including forced vital capacity (FVC) and diffusing capacity of the lung (DCL), as well as echocardiographic study. The efficiency of the treatment was evaluated from changes in FVC, skin score, and disease activity index. The indicators were compared prior to the treatment and one year after the first administration of RTM. The latter was injected with premedication (125–500 mg of methylprednisolone intravenously) 500–1000 mg per administration. The mean dose of RTM was low and amounted to 1.3 g per year. Results. As estimated by the physician, good, satisfactory, no effects were seen in 81.5, 14.8, and 3.7% of the patients, respectively. There was a significant increase in mean FVC one year after the first administration of RTM and a reduction in the total activity of the disease, including skin syndrome. DCL was substantially unchanged in the entire group. In the diffuse and circumscribed forms of the disease, FVC increased significantly and to the same extent. A clinically significant increase in FVC (by 11%) was achieved in patients with a disease duration of ≤5 years and mild lung injury. In people with a more than 5-year disease duration, FVC was initially decreased to a greater extent and the treatment-induced increase was only 3.7%. A significant and permanent decline in peripheral blood B lymphocytes was noted when both the standard dose (2 g) of RTM and its lower doses (0.5–1 g) were administered. RTM treatment was well tolerated, but complicated by mild intercurrent infections in 11% of cases within the first 2 months after RTM administration. Conclusion. The findings substantiate the indications for RTM use primarily in the early stage of the disease. The admittedly low doses of RTM have an inadequate effect if the disease is long-lasting. Further study of dosage regimens for RTM is required within the framework of controlled trials.

Highlights

  • Цель – изучить эффективность и переносимость лечения ритуксимабом (РТМ) у больных системной склеродермией (ССД) с интерстициальным поражением легких (ИПЛ)

  • The efficiency of the treatment was evaluated from changes in forced vital capacity (FVC), skin score, and disease activity index

  • There was a significant increase in mean FVC one year after the first administration of RTM and a reduction in the total activity of the disease, including skin syndrome

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Summary

Оригинальные исследования

Лечение ритуксимабом интерстициального поражения легких при системной склеродермии. Л.П. Отмечено достоверное увеличение среднего значения ФЖЕЛ через год после первого введения РТМ и уменьшение общей активности болезни, включая кожный синдром. Четвертое испытание было проведено по принципу «Подтверждение концепции» (proof-of-concept trial) для начальной первичной оценки безопасности и эффективности РТМ при клинически выраженном интерстициальном поражении легких (ИПЛ), ассоциированном с ССД [21]. Имеющиеся теоретические предпосылки и первые клинические испытания РТМ при ССД свидетельствуют о том, что В-клеточная деплеция может быть эффективной в отношении как подавления активности кожного процесса на ранней стадии болезни, так и при неэффективности предшествующей стандартной терапии ИПЛ [23]. Исходя из этих данных нами было проведено обсервационное изучение РТМ у больных ССД, несмотря на то что в показания для назначения этого препарата данное РЗ не включено. Целью проспективного открытого исследования было изучение эффективности и переносимости лечения РТМ у больных ССД с ИПЛ с оценкой результатов терапии через год.

Дигитальные рубчики
Число больных n
Через год р
Разница значений
Findings
Собственные данные
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