Цертолизумаб пегол в терапии ревматоидного артрита

The paper reviews the literature on the new tumor necrosis factor-α (TNF-α) antagonist certolizumab pegol (CZP). It considers the experience in using the drug in Russia within the framework of the RAPID 2 trial. The currently obtained material suggests that CZP has extended the capacities of RA treatment. The drug may be successfully used both alone and in combination with other disease-modifying anti-rheumatic drugs and it is effective in all degrees of disease activity. The agent is noted for a particularly rapid achievement of its therapeutic effect, early exhibits antidestructive properties, and enables prediction of the long-term results of therapy at a relatively early stage of its use. It is improbable that the administration of CZP versus other TNF-α antagonists in pregnancy may be safer since it does not seem to penetrate the placental barrier. Emphasis is laid on the most convenient method for administration of the drug, namely, its subcutaneous route at large intervals. In this case there may be rare local reactions.Представлен обзор литературы, посвященной новому антагонисту ФНО α - цертолизумабу пеголу (ЦЗП). Рассматривается опыт применения этого препарата в России в рамках исследования RAPID 2. Полученный к настоящему времени материал позволяет считать, что ЦЗП расширил возможности лечения РА. Он может успешно применяться как в виде монотерапии, так и в комбинации с другими базисными препаратами, эффективен при всех степенях активности болезни. Препарат отличается особенно быстрым достижением лечебного эффекта, рано проявляет антидеструктивные свойства, позволяет предсказать отдаленные результаты терапии на относительно раннем этапе назначения. Не исключено, что по сравнению с другими антагонистами ФНО α применение ЦЗП при беременности может оказаться более безопасным, поскольку он, по-видимому, не проходит через плацентарный барьер. Подчеркивается наиболее удобный для пациентов метод введения - подкожный, с большими интервалами. В таком случае наблюдаются редкие местные реакции

Comparative effectiveness of TNF inhibitors and tocilizumab with and without conventional synthetic disease-modifying antirheumatic drugs in a pan-European observational cohort of bio-naive patients with rheumatoid arthritis

Objectives To compare treatment effectiveness in rheumatoid arthritis (RA) patients naïve to biological disease-modifying antirheumatic drugs (bDMARDs) treated with tocilizumab (TCZ) or TNF-inhibitor (TNFi) with (-combo) or without (-mono) conventional synthetic DMARDs (csDMARDs). Methods Patients with RA across 7 European registries, naïve to bDMARDs who initiated treatment with TCZ or TNFi from 2009 to 2016 were included. Drug retention rate was analyzed using Kaplan–Meier and Cox models, and CDAI over time by mixed models. The proportions of patients reaching CDAI low disease activity (LDA) and remission after one year were corrected for attrition. Results 6713 TNFi-combo, 3762 TNFi-mono, 646 TCZ-combo and 384 TCZ-mono were eligible. Crude median retention was 3.67 years (95%CI 3.41-3.83) for TNFi-combo, 4.14 (3.77-4.62) for TNFi-mono, 2.98 (2.76-3.34) for TCZ-combo and 3.63 years (3.34-5.03) for TCZ-mono. After adjustment for covariates, country and year of treatment initiation stratification, hazards of discontinuation were lower for TCZ-mono (0.60, 95% CI 0.52-0.69) and TCZ-combo (0.66, 95% CI 0.54-0.81) compared to TNFi-combo. Adjusted CDAI evolution was not significantly different between groups. CDAI LDA and remission corrected for attrition were similar between TCZ with or without csDMARDs and TNFi-combo. Conclusion In routine care across 7 European countries, the adjusted drug retention, adjusted CDAI over time and attrition-corrected response proportion for RA patients were similar for bio-naïve patients if treated with TNFi-combo, TCZ-combo or TCZ-mono.Peer reviewe

Effectiveness of TNF-inhibitors, abatacept, IL6-inhibitors and JAK-inhibitors in 31 846 patients with rheumatoid arthritis in 19 registers from the 'JAK-pot' collaboration

Background JAK-inhibitors (JAKi), recently approved in rheumatoid arthritis (RA), have changed the landscape of treatment choices. We aimed to compare the effectiveness of four current second-line therapies of RA with different modes of action, since JAKi approval, in an international collaboration of 19 registers. Methods In this observational cohort study, patients initiating tumour necrosis factor inhibitors (TNFi), interleukin-6 inhibitors (IL-6i), abatacept (ABA) or JAKi were included. We compared the effectiveness of these treatments in terms of drug discontinuation and Clinical Disease Activity Index (CDAI) response rates at 1 year. Analyses were adjusted for patient, disease and treatment characteristics, including lines of therapy and accounted for competing risk. Results We included 31 846 treatment courses: 17 522 TNFi, 2775 ABA, 3863 IL-6i and 7686 JAKi. Adjusted analyses of overall discontinuation were similar across all treatments. The main single reason of stopping treatment was ineffectiveness. Compared with TNFi, JAKi were less often discontinued for ineffectiveness (adjusted HR (aHR) 0.75, 95% CI 0.67 to 0.83), as was IL-6i (aHR 0.76, 95% CI 0.67 to 0.85) and more often for adverse events (aHR 1.16, 95% CI 1.03 to 1.33). Adjusted CDAI response rates at 1 year were similar between TNFi, JAKi and IL-6i and slightly lower for ABA. Conclusion The adjusted overall drug discontinuation and 1 year response rates of JAKi and IL-6i were similar to those observed with TNFi. Compared with TNFi, JAKi were more often discontinued for adverse events and less for ineffectiveness, as were IL-6i.Peer reviewe

Effectiveness of tocilizumab with and without synthetic disease-modifying antirheumatic drugs in rheumatoid arthritis : results from a European collaborative study

Objectives To examine the effectiveness of tocilizumab (TCZ) with and without synthetic disease-modifying antirheumatic drugs (sDMARDs) in a large observational study. Methods Patients with rheumatoid arthritis treated with TCZ who had a baseline visit and information on concomitant sDMARDs were included. According to baseline data, patients were considered as taking TCZ as monotherapy or combination with sDMARDs. Main study outcomes were the change of Clinical Disease Activity Index (CDAI) and TCZ retention. The prescription of TCZ as monotherapy was analysed using logistic regression. CDAI change was analysed with a mixed-effects model for longitudinal data. TCZ retention was analysed with a stratified extended Cox model. Results Multiple-adjusted analysis suggests that prescription of TCZ as monotherapy varied according to age, corticosteroid use, country of the registry and year of treatment initiation. The change of disease activity assessed by CDAI as well as the likelihood to be in remission were not significantly different whether TCZ was used as monotherapy or in combination with sDMARDs in a covariate-adjusted analysis. Estimates for unadjusted median TCZ retention were 2.3 years (95% CI 1.8 to 2.7) for monotherapy and 3.7 years (lower 95% CI limit 3.1, upper limit not estimable) for combination therapies. In a covariate-adjusted analysis, TCZ retention was also reduced when used as monotherapy, with an increasing difference between mono and combination therapy over time after 1.5 years (p=0.002). Conclusions TCZ with or without concomitant sDMARDs resulted in comparable clinical response as assessed by CDAI change, but TCZ retention was shorter under monotherapy of TCZ.Peer reviewe

Effectiveness of two different doses of rituximab for the treatment of rheumatoid arthritis in an international cohort : data from the CERERRA collaboration

Background: The approved dose of rituximab (RTX) in rheumatoid arthritis is 1000 mg x 2, but some data have suggested similar clinical efficacy with 500 mg x 2. The purpose of this study was to compare the effectiveness of the regular and low doses given as first treatment course. Methods: Twelve European registries participating in the CERERRA collaboration (The European Collaborative Registries for the Evaluation of Rituximab in Rheumatoid Arthritis) submitted anonymized datasets with demographic, efficacy and treatment data for patients who had started RTX. Treatment effectiveness was assessed by DAS28 reductions and EULAR responses after 6 months. Results: Data on RTX dose were available for 2,873 patients, of whom 2,625 (91.4 %) and 248 (8.6 %) received 1000 mg x 2 and 500 mg x 2, respectively. Patients treated with 500 mg x 2 were significantly older, had longer disease duration, higher number of prior DMARDs, but lower number of prior biologics and lower baseline DAS28 than those treated with 1000 mg x 2. Fewer patients in the low-dose group received concomitant DMARDs but more frequently received concomitant corticosteroids. Both doses led to significant clinical improvements at 6 months. DAS28 reductions at 6 months were comparable in the 2 dose regimens [mean DeltaDAS28 +/- SD -2.0 +/- 1.3 (high dose) vs. -1.7 +/- 1.4 (low dose), p = 0.23 adjusted for baseline differences]. Similar percentages of patients achieved EULAR good response in the two dose groups, 18.4 % vs. 17.3 %, respectively (p = 0.36). Conclusions: In this large observational cohort initial treatment with RTX at 500 mg x 2 and 1000 mg x 2 led to comparable clinical outcomes at 6 months.Peer reviewe

Certolizumab pegol in therapy for rheumatoid arthritis

The paper reviews the literature on the new tumor necrosis factor-α (TNF-α) antagonist certolizumab pegol (CZP). It considers the experience in using the drug in Russia within the framework of the RAPID 2 trial. The currently obtained material suggests that CZP has extended the capacities of RA treatment. The drug may be successfully used both alone and in combination with other disease-modifying anti-rheumatic drugs and it is effective in all degrees of disease activity. The agent is noted for a particularly rapid achievement of its therapeutic effect, early exhibits antidestructive properties, and enables prediction of the long-term results of therapy at a relatively early stage of its use. It is improbable that the administration of CZP versus other TNF-α antagonists in pregnancy may be safer since it does not seem to penetrate the placental barrier. Emphasis is laid on the most convenient method for administration of the drug, namely, its subcutaneous route at large intervals. In this case there may be rare local reactions

Morphometry Results of Formed Osteodefects When Using Nanocrystalline CeO2 in the Early Stages of Regeneration

This paper studies of the use of nanocrystalline cerium dioxide with artificially formed bone tissue defects. The results of morphometry confirmed the antialterative effect in the early stages of the reparative process of damaged bone tissue. When using calcium hydroxide with nanodispersed cerium dioxide, the nature of osteogenesis should be characterized as activated. In case of damage to the dentin of the roots of the teeth, dentinogenesis in presence of CeO2 occurs with the formation of a combined dentin and bone regenerates. Little or no studies of dentinogenesis in presence of CeO2 were performed by other researchers

Tuberculosis And Viral Hepatitis Infection In Eastern Europe, Asia, And Latin America: Impact Of Tumor Necrosis Factor-Α Inhibitors In Clinical Practice

Tumor necrosis factor-α (TNF-α) inhibitors are increasingly becoming the standard of care for treating a number of inflammatory diseases. However, treatment with TNF-α inhibitors carries an inherent risk of compromising the immune system, resulting in an increased susceptibility to infections and malignancies. This increased risk of infection is of particular concern in Asia, Eastern Europe, and Latin America where tuberculosis (TB) and viral hepatitis are endemic. In this brief review, we examine the literature and review the impact of TNF-α inhibitors on the incidence and the reactivation of latent disease with respect to TB, hepatitis C infection, and hepatitis B infection. Our findings show that TNF-α inhibitors are generally safe, if used with caution. Patients should be screened prior to the initiation of TNF-α inhibitor treatment and given prophylactic treatment if needed. In addition, patients should be monitored during treatment with TNF-α inhibitors and after treatment has stopped to ensure that infections, if detected, are treated promptly and effectively. Our analysis is consistent with other reports and guidelines.PubMedScopu