Comparative effectiveness of a second-line biologic in patients with ulcerative colitis: vedolizumab followed by an anti-TNF versus anti-TNF followed by vedolizumab

BackgroundSequential drug treatment with biological agents in ulcerative colitis (UC) is becoming increasingly complex. There are few studies comparing head-to-head outcomes in second-line treatments. The study assesses whether using anti-tumour necrosis factor (anti-TNF)-α therapy following the α4β7 integrin blocker vedolizumab (VDZ) or VDZ after an anti-TNF has more favourable clinical outcomes in UC in a real-world outpatient setting.MethodsPatients with UC who were exposed to first-line anti-TNF (adalimumab or infliximab) or VDZ who subsequently switched to the alternate class between May 2013 and August 2020 were identified by reviewing patient databases at 10 hospitals. Data were collected retrospectively using patient records. Baseline demographics, disease activity indices, biochemical markers, endoscopic Mayo score, colectomy rates, treatment persistence and urgent hospital utilisation composite endpoint (UHUC) rates were examined over a 52-week period.ResultsSecond-line week 52 treatment persistence was higher in the VDZ group (71/81, 89%) versus the anti-TNF group (15/34, 44%; p=0.0001), as were week 52 colectomy-free survival (VDZ: 77/80, 96%, vs anti-TNF: 26/32, 81%; p=0.009), week 52 UHUC survival (VDZ: 68/84, 81%, vs anti-TNF: 20/34, 59%; p=0.002) and week 52 corticosteroid-free clinical remission (CFCR) rates (VDZ: 22/34, 65%, vs anti-TNF: 4/20, 20%; p=0.001).ConclusionCompared with second-line anti TNF usage, the VDZ second-line cohort had significantly higher 52-week treatment persistence, UHUC survival, higher colectomy-free survival rates and higher week 52 CFCR. These data suggest that VDZ is an effective biologic in UC as a second-line therapy after anti-TNF exposure. It highlights the effect of biological order on clinically important outcomes.

Predictors of Sustained Response With Tofacitinib Therapy in Patients With Ulcerative Colitis

Background Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis. We evaluate baseline characteristics as predictors of sustained response and remission in patients with ulcerative colitis receiving tofacitinib maintenance therapy. Methods Patients with clinical response following OCTAVE Induction 1 and 2 entered OCTAVE Sustain and were rerandomized to receive tofacitinib 5 or 10 mg twice daily or placebo. Baseline characteristics were stratified by week 52 efficacy endpoints (remission, sustained remission, clinical response, sustained clinical response). Associations between baseline characteristics and efficacy endpoints were evaluated using logistic regression analyses. Results Overall, 170 of 487 (34.9%) patients were in remission at week 52. In multivariable modeling, endoscopic subscore at baseline of OCTAVE Induction 1 and 2 (2 vs 3; odds ratio [OR], 1.60; 95% confidence interval [CI], 1.06-2.44]), partial Mayo score (<2 vs ≥2; OR, 1.92; 95% CI, 1.27-2.90), and age (per 10-years; OR, 1.19; 95% CI, 1.02-1.39) at baseline of OCTAVE Sustain (following 8 weeks’ tofacitinib induction therapy) were associated with higher odds of remission at week 52. Oral corticosteroid use (OR, 0.63; 95% CI, 0.42-0.96) and C-reactive protein (per unit; OR, 0.94; 95% CI, 0.89-0.99) at baseline of OCTAVE Sustain were associated with reduced likelihood of remission at week 52. In general, opposite associations were observed for time to loss of response. Conclusion Patients with greater clinical improvement after 8 weeks of tofacitinib induction therapy are more likely to maintain response or remission with tofacitinib regardless of dose received during maintenance, highlighting the importance of a robust response to induction therapy.

The Association between Temperament, Chronotype, Depressive Symptoms, and Disease Activity among Patients with Inflammatory Bowel Disease—A Cross-Sectional Pilot Study

The psychological aspect may play an important role in ulcerative colitis (UC) and Crohn’s disease (CD). The aims of this study were to explore the differences between patients with UC and CD regarding chronotype, temperament and depression, and to assess the psychological factors mentioned as predictors of disease activity. In total, n = 37 patients with UC and n = 47 patients with CD were included in the study. They underwent a clinical assessment, including the Mayo score or Crohn Disease Activity Index (CDAI), and completed questionnaires: a sociodemographic survey, Formal Characteristics of Behavior–Temperament Inventory (FCB-TI), Chronotype Questionnaire (CQ), and the Beck Depression Index II (BDI). The Sensory Sensitivity score was higher among patients with CD than UC (p = 0.04). The emotional reactivity and endurance scores were higher among women than men with CD (p = 0.028 and p = 0.012 respectively). CQ Morningness–Eveningness (ME) correlated with Endurance (p = 0.041), Emotional Reactivity (p = 0.016), and Activity (p = 0.004). ME correlated with Rhythmicity among CD patients (p = 0.002). The Mayo score was predicted by Perseverance. The CDAI score was predicted by the BDI score. The pattern of the relationship between chronotype and temperament may differentiate patients with UC and CD. Personal disposition may play a role in the clinical assessment of patients with IBD.

Predictive value of fibrinogen in identifying inflammatory bowel disease in active stage

Background We aimed to externally validate for the first time the diagnostic ability of fibrinogen to identify active inflammatory bowel disease (IBD). Methods The research totally involved 788 patients with IBD, consisted of 245 ulcerative colitis (UC) and 543 Crohn’ s disease (CD). The Mayo score and Crohn disease activity index (CDAI) assessed disease activity of UC and CD respectively. The independent association between fibrinogen and disease activity of patients with UC or CD was investigated by multivariate logistic regression analyses. Area under the receiver operating characteristic curve (AUROC) assessed the performance of various biomarkers in discriminating disease states. Results The fibrinogen levels in active patients with IBD significantly increased compared with those in remission stage (P < 0.001). Fibrinogen was an independent predictor to distinguish disease activity of UC (odds ratio: 2.247, 95% confidence interval: 1.428–3.537, P < 0.001) and CD (odds ratio: 2.124, 95% confidence interval: 1.433–3.148, P < 0.001). Fibrinogen was positively correlated with the Mayo score (r = 0.529, P < 0.001) and CDAI (r = 0.625, P < 0.001). Fibrinogen had a high discriminative capacity for both active UC (AUROC: 0.806, 95% confidence interval: 0.751–0.861) and CD (AUROC: 0.869, 95% confidence interval: 0.839–0.899). The optimum cut-off values of fibrinogen 3.22 was 70% sensitive and 77% specific for active UC, and 3.87 was 77% sensitive and 81% specific for active CD respectively. Conclusions Fibrinogen is a convenient and practical biomarker to identify active IBD.

Long-term, Real-life, Observational Study in Treating Outpatient Ulcerative Colitis with Golimumab

Background and Aims: Several studies have found Golimumab (GOL) effective and safe in the short-term treatment of ulcerative colitis (UC), but few long-term data are currently available from real world. Our aim was to assess the long-term real-life efficacy and safety of GOL in managing UC outpatients in Italy. Methods: A retrospective multicenter study assessing consecutive UC outpatients treated with GOL for at least 3-month of follow-up was made. Primary endpoints were the induction and maintenance of remission in UC, defined as Mayo score ≤2. Several secondary endpoints, including clinical response, colectomy rate, steroid free remission and mucosal healing, were also assessed during the follow-up. Results: One hundred and seventy-eight patients were enrolled and followed up for a median (IQR) time of 9 (3-18) months (mean time follow-up: 33.1±13 months). Clinical remission was achieved in 57 (32.1%) patients: these patients continued with GOL, but only 6 patients (3.4%) were still under clinical remission with GOL at the 42nd month of follow-up. Clinical response occurred in 64 (36.4%) patients; colectomy was performed in 8 (7.8%) patients, all of them having primary failure. Steroid-free remission occurred in 23 (12.9%) patients, and mucosal healing was achieved in 29/89 (32.6%) patients. Adverse events occurred in 14 (7.9%) patients. Conclusions: Golimumab does not seem able to maintain long-term remission in UC in real life. The safety profile was good.

Long-Term Outcomes and Predictive Factors of Hospitalized Patients with Severe Ulcerative Colitis Treated with Intravenous Corticosteroids

Background and Aims: Treatment with intravenous corticosteroids (IVCS) is a mainstay in the management of acute severe ulcerative colitis (UC). Although most patients respond to IVCS, little is known about the long-term outcomes. In this study, we assessed the long-term outcomes of IVCS in a real-life cohort. Methods: Disease activity, clinical relapse (partial Mayo score >4), the need for steroids or other maintenance therapies and the rates of colectomy and re-hospitalization were evaluated in consecutive patients admitted to the Tor Vergata University hospital between 2010 and 2020 for acute severe UC who responded to IVCS. Results: Eighty-eight patients were followed up with for a median period of 46 (range 6–133) months. Of these, 56 (64%) patients were treated with 5-aminosalycilic acid and 32 (36%) with immunomodulators or biologics after discharge. A total of 60 out of 88 patients (68%) relapsed, 28 (32%) were re-hospitalized, and 15 (17%) underwent a colectomy with no difference between the two maintenance therapy groups. The multivariate analysis showed that patients in clinical remission 6 months after discharge had a lower risk of relapse during the follow-up. Conclusions: Nearly two-thirds of patients with acute UC responding to IVCS experienced relapse after a median follow-up of 4 years, and this was not influenced by the maintenance therapy.

Translating Results from VARSITY to Real World: Adalimumab vs Vedolizumab as First-line Biological in Moderate to Severe IBD

Background Selecting a first-line therapy remains challenging in IBD. Adalimumab (ADM) and vedolizumab (VDZ) effectively lead to endoscopic remission in moderate to severe IBD. The VARSITY trial showed superiority of VDZ over ADM in ulcerative colitis (UC) regarding clinical remission and endoscopic improvement at week 52. We explored these results in a real-world setting of UC and Crohn’s disease (CD). Methods This retrospective study followed a cohort of biologic-naïve patients starting ADM or VDZ from 2015-2019. Patients had moderate to severe disease (endoscopic Mayo score ≥2 for UC, presence of ulcerations for CD) prior to therapy initiation. For UC, endoscopic remission (endoscopic Mayo score 0) and improvement (endoscopic Mayo score ≤1) at week 52 were assessed. For CD, endoscopic remission (absence of ulcerations) and improvement (markedly better endoscopy despite ulcerations) at weeks 26-52 were studied. Treatment persistence was also evaluated. Results In total, 195 biologic-naïve patients (109 UC; 86 CD) were included. In UC, VDZ was superior to ADM regarding endoscopic remission (29% vs 11%, P = .03), endoscopic improvement (51% vs 26%, P = .01) at week 52, and treatment persistence (P = .04). In CD, no differences in endoscopic remission (VDZ 48% vs ADM 60%; P=0.37), improvement (VDZ 76% vs ADM 77%; P = 1.00), or treatment persistence (P=0.43) at weeks 26-52 were seen. Safety profiles were similar in UC and CD. Conclusions This real-world cohort study of biologic-naïve IBD patients found VDZ to be superior to ADM as first-line treatment for patients with UC—but not CD—regarding endoscopic remission at week 52 and treatment persistence.

Effectiveness of treatment of moderate ulcerative colitis with prolonged mesalazine in real clinical practice

Introduction. Ulcerative colitis (UC) is one of the severe therapeutic diseases. High doses of oral granular mesalazine are required to maintain clinical and endoscopic remission of UC, which may be sufficient and supposedly more acceptable for patients, as some studies showed that adherence to topical therapy is significantly lower than to oral 5-ASA drugs.Objective of the study. To evaluate the efficacy of therapy of patients with moderate left-sided ulcerative colitis (UC) and pancolitis receiving prolonged-release ethylcellulose-coated mesalazine.Materials and methods. The evaluation of the outcomes of treatment of UC patients who received prolonged-release mesalazine was carried out. We examined 87 patients with UC who received granular ethylcellulose-coated mesalazine, of those 38 (43.7%) men and 49 (56.3%) women. The average age of the enrolled patients was 38.3 ± 12.6 years.Results and discussion. After 2 weeks from the beginning of therapy with prolonged-release mesalazine, the majority of patients – 71 (81.6%) responded to the therapy. After 12 weeks, 71 (81.6%) of 87 UC patients, who responded to therapy with prolongedrelease mesalazine, remained in clinical remission. On average, the Mayo score in the group decreased from 7.6 ± 0.99 to 2.6 ± 0.25 points. There was a significant decrease in CRP, ESR, leukocytosis, and fecal calprotectin. After 26 weeks, Mayo score in the group of patients remained on average at the level of 2.2–2.3 points. The number of UC patients with colon mucosal healing was 32 (36.8%) patients. A year after the start of therapy with prolonged-release mesalazine, 69 (79.3%) UC patients who responded to therapy had a clinical remission, of those 32 (36.8%) patients had a clinical and endoscopic remission. During the year of observation, no case of surgical intervention or re-hospitalization due to exacerbation of the disease was recorded in patients with UC who achieved remission.Conclusions. Treatment of moderate active UC should begin with oral mesalazine ≥ 3 g per day in combination with topical mesalazine. The prolonged-release mesalazines are the most preferred

An Atypical Type of Monteggia Equivalent: A Case Report

Introduction:Management of Mmonteggia fractures has always been debatable; Nnumerous variants have been described in the literature since its first description in 1814. We report a new variant of classical Mmonteggia fracture in a 33-year-old male. Case Presentation: A 33-year old male was brought to the emergency room with an alleged history of assault and was managed with an external wound. Antero-Pposterior and lateral radiographs showed segmental ulna fracture and radial head dislocation. The Ppatient was managed surgically with open reduction internal fixation with reconstruction plate for segmental ulna and closed reduction of radial head was attempted after achieving an anatomical reduction of the ulna. Close attention was paid to the early post-operative mobilization of the elbow joint with the help of a Hinged elbow brace and terminal functional outcome re re-evaluated at 6six months with a DASH score of 11 and MAYO score of 92. Conclusion: We report a rare type 1 monteggia equivalent not described in the literature. Despite the variability of the monteggia equivalents, the principle of management remains the same. Early mobilization of the elbow is of utmost importance to avoid post-operative stiffness. Keywords: Atypical, Equivalent, Monteggia, Segmental.

Predictors of Surgical Intervention in Patients with Inflammatory Bowel Disease

Background Inflammatory bowel disease (IBD) is comprised of two major disorders: Ulcerative Colitis and Crohn’s disease. Ulcerative Colitis affects the colon, where as Crohn’s disease can involve any component of the gastrointestinal tract from the mouth to the perianal area. These disorders have somewhat different pathologic and clinical characteristics, but with substantial overlap; their pathogenesis remains poorly understood. Objective To determine & detect different predictors that help us to characterize patients with high probability of undergoing surgical intervention for inflammatory bowel diseases. Patients and Methods The present study was designed to detect & identify possible factors that can be used to predict surgical intervention in patients with IBD. The present study was a case control study that was conducted on 80 patients with inflammatory bowel disease (either controlled by medical treatment or needed surgical intervention as a part of disease control) who were recruited form Ain-Shams university hospitals and El Quabbary general hospital in Alexandria. In the present study, the mean age of the included patients was 36.67 ±8.5 years old and 50% of the patients were males. The mean age at the onset of the disease was 25.81 ±6.8 years old. Results In the present study, there were statistically significant differences between surgical and medical patients in terms of CDAI for CD (p &lt; 0.001) and Mayo score for UC (p &lt; 0.001). Surgical patients were more likely to have higher scores. CDAI and Mayo score were negative predictors of surgical treatment. CDAI score &gt; 287 and Mayo score &gt; 8.5 achieved high sensitivity and specificity for the detection of surgical treatment. In the present study, we found that there was statistically significant differences between surgical and medical patients in terms of Stool Calprotectin level. Surgical patients were more likely to have higher Stool Calprotectin level. Stool Calprotectin level was negative predictor of surgical treatment at a level of &gt; 341.5 microgm/gm with high sensitivity and specificity. Conclusion Surgical treatment is a common outcome in IBD. Certain clinical features and the extent of disease are risk factors for surgical intervention. Our study indicates that smoking, Chron’s disease, perianal disease, granulomas, higher severity scores, higher stool Calprotectin level, CRP, and ESR were associated with higher risks of surgical intervention. In addition, smoking, peri-anal disease, CDAI, Mayo score, Stool Calprotectin level, and CRP level were predictors of surgical treatment. The findings of our analysis have implications for practice, particularly in the promotion of preoperative individualized risk prediction. The ability to predict which patients will need surgery and target more intensive, early treatment to that group would be invaluable. Further research through large prospective cohort studies is needed to confirm our findings and conclusions.