BACKGROUND AND AIMS: Tofacitinib (TFB) appears to be effective in the treatment of ulcerative colitis (UC); however, available real-world studies are limited by cohort size. TFB could be an option in the treatment of acute severe ulcerative colitis (ASUC). We aimed to investigate efficacy and safety of TFB in moderate-to-severe colitis and ASUC. METHODS: This retrospective, international cohort study enrolling UC patients with ≥6-week follow-up period was conducted from February 1 to July 31, 2022. Indications were categorized as ASUC and chronic activity (CA). Baseline demographic and clinical data were obtained. Steroid-free remission (SFR), colectomy, and safety data were analyzed. RESULTS: A total of 391 UC patients (median age 38 [interquartile range, 28-47] years; follow-up period 26 [interquartile range, 14-52] weeks) were included. A total of 27.1% received TFB in ASUC. SFR rates were 23.7% (ASUC: 26.0%, CA: 22.8%) at week 12 and 41.1% (ASUC: 34.2%, CA: 43.5%) at week 52. The baseline partial Mayo score (odds ratio [OR], 0.850; Pâ =â .006) was negatively associated with week 12 SFR, while biologic-naïve patients (OR, 2.078; Pâ =â .04) more likely achieved week 52 SFR. The colectomy rate at week 52 was higher in ASUC group (17.6% vs 5.7%; Pâ <â .001) and decreased with age (OR, 0.94; Pâ =â .013). A total of 67 adverse events were reported, and 17.9% resulted in cessation of TFB. One case of thromboembolic event was reported. CONCLUSIONS: TFB is effective in both studied indications. TFB treatment resulted in high rates of SFR in the short and long terms. Higher baseline disease activity and previous biological therapies decreased efficacy. No new adverse event signals were found.
BACKGROUND: Endoscopic-post-operative-recurrence [ePOR] in Crohn's disease [CD] after ileocecal resection [ICR] is a major concern. We aimed to evaluate the effectiveness of early prophylaxis with biologics and to compare anti-tumour necrosis factor [anti-TNF] therapy to vedolizumab [VDZ] and ustekinumab [UST] in a real-world setting. METHODS: A retrospective multicentre study of CD-adults after curative ICR on early prophylaxis was undertaken. ePOR was defined as a Rutgeerts score [RS] ≥ i2 or colonic-segmental-SES-CD ≥ 6. Multivariable logistic regression was used to evaluate risk factors, and inverse probability treatment weighting [IPTW] was applied to compare the effectiveness between agents. RESULTS: The study included 297 patients (53.9% males, age at diagnosis 24 years [19-32], age at ICR 34 years [26-43], 18.5% smokers, 27.6% biologic-naïve, 65.7% anti-TNF experienced, 28.6% two or more biologics and 17.2% previous surgery). Overall, 224, 39 and 34 patients received anti-TNF, VDZ or UST, respectively. Patients treated with VDZ and UST were more biologic experienced with higher rates of previous surgery. ePOR rates within 1 year were 41.8%. ePOR rates by treatment groups were: anti-TNF 40.2%, VDZ 33% and UST 61.8%. Risk factors for ePOR at 1 year were: past-infliximab (adjusted odds ratio [adj.OR] = 1.73 [95% confidence interval, CI: 1.01-2.97]), past-adalimumab [adj.OR = 2.32 [95% CI: 1.35-4.01] and surgical aspects. After IPTW, the risk of ePOR within 1 year of VDZ vs anti-TNF or UST vs anti-TNF was comparable (OR = 0.55 [95% CI: 0.25-1.19], OR = 1.86 [95% CI: 0.79-4.38]), respectively. CONCLUSION: Prevention of ePOR within 1 year after surgery was successful in ~60% of patients. Patients treated with VDZ or UST consisted of a more refractory group. After controlling for confounders, no differences in ePOR risk were seen between anti-TNF prophylaxis and other groups.
Biological Products , Crohn Disease , Adult , Female , Humans , Male , Biological Products/therapeutic use , Crohn Disease/drug therapy , Crohn Disease/prevention & control , Crohn Disease/surgery , Retrospective Studies , Treatment Outcome , Tumor Necrosis Factor Inhibitors/therapeutic use , Ustekinumab/therapeutic use , Young Adult
BACKGROUND: Tofacitinib is a selective immunosuppressant, the first representative of the inhibitors of the janus kinase family, which has high selectivity against other kinases of the human genome. According to the results of the study, tofacitinib inhibits JAK-1, JAK-2, and in high concentrations - JAK-3 and tyrosine kinase-2. The drug is registered in Russia for the treatment of patients with ulcerative colitis. According to the OCTAVE Sustain study, steroid-free remission in patients with ulcerative colitis receiving tofacitinib at a dose of 10 and 20 mg per day is 27.7% and 27.6%, respectively. OBJECTIVE: To identify the frequency of steroid-free remission in patients with ulcerative colitis receiving tofacitinib in real clinical practice. METHODS: In the Department of Inflammatory Bowel Diseases of the Moscow Clinical Scientific and Practical Center named after A. S. Loginov, 58 patients with ulcerative colitis (UC) who received tofacitinib were observed. The effectiveness of therapy was evaluated (the value of the Mayo index less than 2, ESR, CRP, hemoglobin, fecal calprotectin (FCP) and the need for the appointment of glucocorticosteroids (GCS). The follow-up period was 12 months from the start of tofacitinib therapy. RESULTS: During the follow-up period, out of 58 (100%) UC patients treated with tofacitinib, 9 (15.5%) patients did not respond to therapy. A prolonged induction course at a dose of 20 mg of tofacitinib was required in 14 (24.1%) patients who had previously received anti-TNF-α drugs. All patients at the time of initiation received GCS at an average therapeutic dose of 40 mg. After the induction course, corticosteroids were discontinued in 49 (100%) patients who responded to treatment. All patients achieved remission within 12 months of therapy (Meyo < 2). Repeated administration of corticosteroids for exacerbation or "eluding" of the response to tofacitinib was required in 11 of 49 (22.4%) patients. CONCLUSION: Steroid-free remission in patients with ulcerative colitis, receiving tofacitinib for 12 months, in real clinical practice is 77.6%.
BACKGROUND: The objectives of the treatment of patients with ulcerative colitis (UC) in accordance with the STRIDE-I provision, involves endoscopic healing of the colon mucosa. Histological remission is associated with endoscopic healing, which can be a predictor of long-term results. Biological and cellular therapy is most effective in the early stages of the disease. OBJECTIVE: To assess the depth of histological remission with the duration of UC. METHODS: The biopsy material of 75 patients with total or left-sided UC of moderate severity and severe severity aged from 22 to 56 years (average age 31 ± 2.5 years), who were divided into groups depending on the therapy, was studied. The first group of patients with UC aged 22 to 51 years (Me-32) (n = 29) received anti-inflammatory therapy using mesenchymal stromal cell culture (MSCs) 2 million/kg; the second group of patients with UC (n = 27) aged 24 to 56 years (Me-38) received vedolizumab (VDB) according to the recommended scheme, the third group of patients with UC (n = 19) aged 27 to 52 years (Me-31) received MSCs+VDB. The achievement of histological remission was assessed by the score of Geboes (SG). RESULTS: In 1st group, patients who achieved histological remission (SG1) with a disease duration of more than 5 years - 14 (48.3%) patients, less than 5 years - 5 (17.2%) (95% CI 1.256 - 19.293; x2-7.635; p = 0.006). In the 2nd group of patients who achieved histological remission (SG1) with a disease duration of more than 5 years - 15 (55.5%) patients, less than 5 years - 4 (14.9%) (95% CI 1.262 - 20.615; x2-7.026; p = 0.009). In the 3rd group of patients who achieved histological remission (SG1) with a disease duration of more than 5 years - 4 (21.1%) patients, less than 5 years - 7 (36.8%) (95% CI 1.080 - 138.995; x2-4.968; p = 0.026). CONCLUSION: A statistically significant majority of patients who achieved histological remission, regardless of the therapy, had a disease duration of less than 5 years.
BACKGROUND: Anxiety and depression occur in a significant number of patients with inflammatory bowel diseases (IBD). The prevalence of anxiety and / or depression is 13-44.4% in patients with IBD compared to 4.4% among the world population. OBJECTIVE: To identify the frequency of anxiety and depression in patients with inflammatory bowel diseases in the Moscow Clinical Scientific Center named after A. S. Loginov. METHODS: A questionnaire was conducted on the Hospital Anxiety and Depression Scale (HADS) questionnaire for 370 patients with moderate to severe UC during the period of exacerbation of the disease. RESULTS: Of the 370 patients with UC, 283 (76.48%) had clinical and subclinical signs of anxiety and depression. Subclinical depression was noted in 76 (26.8%), clinically pronounced depression - 11 (3.4%), signs of anxiety had higher indicators-subclinical anxiety was found in 172 (60.8%) of the surveyed patients, pronounced clinical anxiety - in 24 (8.4%) patients with UC. Statistically significant correlations of average strength between the indicators of adherence according to the Morisky - Green questionnaire with scores on the HADS scale, both for anxiety and depression (p < 0.001, r - 0.6299) were revealed Among patients with anxiety and depression, the ratio of patients with high adherence to therapy (HAT) and low adherence to therapy (LAT) was 204 (55,1%) 79 (21,4%), accordingly. When comparing the degree of adherence depending on the presence of anxiety and depression, we found that HAT was associated with anxiety and depression in patients with UC (OR = 0.024; 95% CI 0.003-0.186; p < 0.001). CONCLUSION: The prevalence of anxiety and/or depression is 77% in patients with IBD during an exacerbation in the Moscow Clinical Scientific Center named after A. S. Loginov.
BACKGROUND: Goal: To identify the relationship between the level of immunoglobulins G and E and the development of adverse reaction (AR) in patients with ulcerative colitis (UC) receiving original infliximab (IFÐ¥) and infliximab biosimilar (BS). METHODS: 35 UC patients with moderate to severe course of the disease (according to Truelove-Witts) who received maintenance therapy with IFÐ¥ at a standard dose of 5 mg/kg of body weight for a year were retrospectively analyzed. There were 16 men (45.7%), 19 women (54.3%). The average age is 34±4.2 years. The duration of the anamnesis was from 3 to 7 years. Patients were divided into 3 groups depending on the development of AR and the received biological drug, without taking into account concomitant anti-inflammatory therapy. The 1st group (n=14) alternated the introduction of the original IFÐ¥ and its BS; The 2nd group (n=7) consisted of patients alternating between the original IFÐ¥ and BS, in whom AR was registered; the 3rd group (n=14) received BS by one trade name. Using enzyme immunoassay, the level of immunoglobulins in the groups of patients was assessed. RESULTS: In the 1st and 3rd groups, AR was not observed. AR in 2nd group was characterized by: bronchospasm 3 (42.8%), Quincke's edema 1 (14.3%), urticaria 1 (14.3%), rhinitis 1 (14.3%), anaphylactic shock 1 (14.3%). In patients of 1st group, the level of IgE is 44.8 ± 5.1 IU/ml, IgG is 16.5 ± 1.7 g/l. In 2nd group -IgE-44.5 ± 11.7 IU / ml, IgG-26.1 ± 2.1 g/l, while in patients in group 3-IgE - 31.5 ± 3.04 IU/ml, IgG - 9.46 ± 1.01 g/l. It was reliably established that the highest level of IgG was observed in the 2nd group, while in the 3rd group it was minimal (p < 0.05). The IgG level in 1st group is higher than in 3rd group, although in both groups the IgG level was within the reference values. In all groups, the IgE value remained normal. CONCLUSION: AR on the background of therapy with IFL and biosimilars are not associated with an increase in the level of IgE, but are caused by an increase in the level of IgG. The alternation of the original drug and the biosimilar increases the risk of developing AR due to increased IgG levels. Treatment with a biosimilar by one trade name does not increase the risk of developing AR.
One of the dysbioses often observed in Crohn's disease (CD) patients is an increased abundance of Escherichia coli (10-100 fold compared to healthy individuals) (Gevers et al., 2014). The data reported is a large-scale proteome profile for E. coli isolates collected from CD patients and healthy individuals. 43 isolates were achieved from 30 CD patients (17 male, 12 female, median age 30) and 19 isolates from 7 healthy individuals (7 male, median age 19). Isolates were cultivated on LB medium at aerobic conditions up to medium log phase. Protein extraction was performed with sodium deoxycholate (DCNa) and urea, alcylation with tris(2-carboxyethyl)phosphine and iodacetamide. Protein trypsinolysis was performed as described in (Matyushkina et al., 2016). Total cell proteomes were analysed by shotgun proteomics with HPLC-MS/MS on a maXis qTOF mass-spectrometer. The data including HPLC-MS/MS raw files and exported Mascot search results was deposited to the PRIDE repository project accession: PXD010920, project https://doi.org/10.6019/PXD010920.
