Aim. To evaluate the efficacy and safety of adalimumab (ADA) in patients with Crohn’s disease (CD) treated at the Department of Inflammatory Bowel Diseases, Moscow Clinical Research and Practical Center, and to determine the predictors of a therapy response. Subjects and methods. All the patients with CD treated with ADA were followed up for at least 6 months or until the drug was discontinued. Therapeutic effectiveness was evaluated at 4 weeks and 6 months after the initiation of treatment and at the end of a follow-up. Complete intestinal mucosal healing was assessed at 3 and 12 months following treatment initiation. Univariate and multivariate analyses were used to determine the predictors of treatment response. Results. A clinical analysis covered 70 patients (57.1% male); the follow-up period averaged 112 weeks. Perianal fistulas were at baseline established in 22 (31.4%) patients with CD. 12 (17.4%) patients had been previously treated with infliximab (INF), 7 of them discontinued the drug for secondary loss of response and 5 for adverse reactions. 68 (97.1%) patients responded to an induction course of ADA. At 4 weeks, 6 months, and at the end of the follow-up, clinical remission occurred in 66.7, 80.4 and 67.4 % of patients with luminal CD and in 45.4, 36.5, and 36.4% of those with perianal CD, respectively. At 3 and 12 months and at the end of the follow-up, there was complete healing of the intestinal mucosa in 23.5, and 41.2 and 29.5% of cases, respectively. Six (8.8%) patients responding to the induction course needed to be optimized with ADA to 40 mg weekly. The time interval between treatment initiation and dose optimization averaged 30 weeks (range 12-120 months). There were 15 (21,4%) adverse events that were responsible for ADA discontinuation in 3 (4,2%) patients. Conclusion. The findings demonstrate the efficacy and safety of ADA used in clinical practice.
Aim. To compare the effectiveness of the effect of combination therapy (local and systemic administration) with bone marrow mesenchymal stromal cells (MSC), anticlitokine therapy with infliximab (IFX), and antibiotic (AB)/immunosuppressive (IS) therapy on the frequency of healing of simple perianal fistulas in Crohn's disease. Materials and methods. In our study, the 1-st group of patients aged 19 to 58 years (Me-29) (n = 12) received MSCs culture systemically according to the scheme and locally. The 2-nd group of patients with CD (n = 10) from 20 to 68 years old (Me-36) received anticytokine therapy with infliximab (IFX) according to the scheme. The 3-d group of patients with CD (n=14) from 20 to 62 years old (Me-28) received antibiotics (AB) and immunosuppressors (IS). Efficacy was assessed by the index of perianal activity of Crohn's disease (PCDAI) and the frequency of relapses. Results. After 12 weeks among patients of the 1-st group, healing of simple fistulas was noted in 8/12 patients (66.6%), in the 2-nd group in 6/10 (60.0%) In the 3-d group, in 1/14 patients (7.14%). After 6 months in the 1-st group of patients, healing of simple fistulas was preserved in 8/12 (66.6%), in the 2-nd group - in 6/10 (60.0%). In the 3-d group - in 1/14 patients (7.14%). After 12 months in the 1-st group, healing of simple fistulas was preserved in 7/12 (58.3%), in the second group - in 6/10 (60.0%). In the 3-d group - in 2/14 patients (14.3%). After 24 months, among the patients of the 1-st group, fistula closure was maintained in 5/12 patients (41.6%), in the 2-nd group - in 4/10 (40.0%). In the 3-d group - in 0/14 patients (0.0%). Conclusion. Combined cellular and anticytokine therapy of CD with perianal lesions significantly contributes to the more frequent and prolonged closure of simple fistulas, as compared to antibiotics/immunosuppressors, and to a decrease in the frequency of recurrence of the disease.
This article was designed to be the overview of the current literature publications concerning the identification of the genetic markers of susceptibility to the noise-induced loss of hearing. The analysis of these data has demonstrated that the major gene polymorphisms associated with the development of this pathological condition are localized in the genes encoding for the antioxidant systems, potassium homeostasis, and adhesion molecules as well as in the genes involved in intercellular coupling, the mechanisms underlying the cellular response to stress, activation and regulation of heat shock proteins, and signaling function of the immune system. It is concluded that the further investigations into the genetic aspects of the full-genome sequencing techniques and the search for genomic associations could greatly contribute to the development of personalized medicine and the reduction of risks of occupational noise-induced sensorineural impairment of hearing.
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