Sa555 COLECTOMY-FREE DRUG SURVIVAL OF USTEKINUMAB IN ULCERATIVE COLITIS: A REAL-WORLD, MULTICENTER COHORT STUDY IN THE UNITED STATES

2021 ◽  
Vol 160 (6) ◽  
pp. S-549
Author(s):  
Rahul S. Dalal ◽  
Scott Esckilsen ◽  
Edward L. Barnes ◽  
Jordan C. Pruce ◽  
Jenna Marcus ◽  
...  
Keyword(s):  
United States ◽  
Ulcerative Colitis ◽  
Cohort Study ◽  
Real World ◽  
The United States ◽  
Free Drug ◽  
Multicenter Cohort Study ◽  
Drug Survival ◽  
Multicenter Cohort

scholarly journals P324 Predictors of corticosteroid-free remission after initiation of ustekinumab for ulcerative colitis: a real-world, multicenter cohort study in the United States

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S348-S349
Author(s):  
R Dalal ◽  
S Esckilsen ◽  
E Barnes ◽  
E McClure ◽  
H Goodrick ◽  
...  
Keyword(s):  
United States ◽  
Ulcerative Colitis ◽  
Logistic Regression ◽  
Cohort Study ◽  
Real World ◽  
The United States ◽  
Multicenter Cohort Study ◽  
Mayo Score ◽  
Multicenter Cohort

Abstract Background Clinical trial data has demonstrated the efficacy of ustekinumab (UST) for the treatment of ulcerative colitis (UC), however real-world clinical outcomes data are limited. We therefore performed a real-world multicenter cohort study to identify predictors of corticosteroid-free clinical remission after initiation of ustekinumab for UC. Methods This is a retrospective cohort study of adult UC patients initiating UST between 1/1/2016 and 11/1/2020 at three large IBD referral centers in the United States. Patients with prior colectomy and those receiving UST for primarily non-UC indications were excluded. Electronic health records were reviewed to obtain clinical data. Independent variables present at UST induction included demographics, disease duration, extraintestinal manifestations, current/prior IBD medications, substance use (cigarettes, cannabis, or opioids), last endoscopic extent/severity, last serum albumin and C-reactive protein (within 3 months prior to induction), and daily bowel frequency. The primary outcome was corticosteroid-free remission (i.e. simple clinical colitis activity index [SCCAI] or 9-point Mayo score of <3) 12-16 weeks after induction. Secondary outcomes included clinical response (reduction of SCCAI or Mayo score by >2 points from baseline) 12-16 weeks after induction and UST failure (i.e. UST discontinuation or colectomy due to uncontrolled disease) within 52 weeks after induction. Multivariable logistic regression was used to identify factors associated with remission. Results We identified 108 UC patients who initiated UST. Median age at induction was 39 years (IQR 30-56 years), 91.7% (99/108) of patients had prior anti-TNF exposure, and 60.2% (65/108) had prior anti-TNF and anti-integrin exposure (Table 1). Of 101 patients with available clinical follow-up data, 39.6% achieved remission and 51.5% had clinical response 12-16 weeks after induction. UST failure occurred in 41.1% (23/56 with sufficient follow-up) within 52 weeks. Adverse events were reported in 3.0% (3/101; rash, urinary tract infection, and C. difficile infection). After multivariable logistic regression, prior anti-TNF and anti-integrin exposure (OR 0.31, 95% CI 0.11-0.86), Mayo endoscopic severity >1 (OR 0.30, 95% CI 0.10-0.88), and bowel frequency (OR 0.84, 95% CI 0.72-0.98) were inversely associated with remission (Table 2). Conclusion In this multicenter cohort, nearly 40% of UC patients achieved corticosteroid-free remission 12-16 weeks after UST induction. Prior exposure to both anti-TNF and anti-integrin therapies, endoscopic severity, and daily bowel frequency were associated with failure to achieve remission. Prospective studies are needed to optimize management strategies for UC patients with failure of two biologic classes.

scholarly journals P261 Predictors and outcomes of ustekinumab dose escalation to every 4 or every 6 weeks in ulcerative colitis: a multicenter cohort study in the United States

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S296-S298
Author(s):  
R Dalal ◽  
S Esckilsen ◽  
E Barnes ◽  
J Pruce ◽  
J Marcus ◽  
...  
Keyword(s):  
United States ◽  
Ulcerative Colitis ◽  
Cohort Study ◽  
Adverse Events ◽  
Dose Escalation ◽  
Clinical Remission ◽  
The United States ◽  
Multicenter Cohort Study ◽  
Loss Of Response ◽  
Multicenter Cohort

Abstract Background Patients with ulcerative colitis (UC) on ustekinumab (UST) therapy may have suboptimal response to standard every 8 week (q8w) dosing. Empiric dose escalation to q4w or q6w is common, but the efficacy of these strategies are unknown in UC. We performed a multicenter cohort study to identify predictors and outcomes of UST dose escalation in UC. Methods This retrospective cohort study included adults initiating UST for UC (ICD-10-CM 51x) at three academic medical centers in the United States 1/1/2016-11/1/2021. Patients with prior colectomy were excluded. Disease activity was assessed using the 9-point Mayo score or simple clinical colitis activity index (SCCAI) in electronic health records. Independent variables included demographics, UC duration, extraintestinal manifestation, medication/substance use history, endoscopic extent/severity, reason for escalation, intravenous (IV) reinduction, dose interval, albumin, C-reactive protein, and bowel frequency. The primary outcome was steroid-free clinical remission (SCCAI/Mayo <3 points) 12–16 weeks after escalation. Secondary outcomes were clinical response (reduction in SCCAI/Mayo by ≥3 points from baseline) at 12–16 weeks and time to escalation. Additional endpoints included endoscopic response, failure within 16 weeks (treatment discontinuation or colectomy), improvement in fecal calprotectin, UC hospitalisation, and adverse events. Multivariable logistic and cox regression were used to identify factors associated with remission and time to escalation, respectively. Results 108 UC patients initiated UST: 91.7% had prior anti-TNF exposure and 57.4% were taking oral steroids (Table 1). 39.6% (40/101 with data) achieved remission 12–16 weeks after induction. 42.6% (46/108) were escalated to q4w (n=33) or q6w (n=13) after median of 95 days (IQR 65–208 days) primarily for no/minimal response to induction (22/46) or loss of response (20/46) (Fig 1A). 55.0% (22/40 with data) achieved remission at 12–16 weeks, 67.5% (27/40) had response, 56.3% (9/16 with data) had endoscopic response (Table 2), and 30.0% (12/40) had treatment failure (Fig 1B). 10.0% (4/40) were hospitalised after median of 80 days and 5.0% (2/40) had adverse events (urinary tract infection and C. difficile infection). After multivariable analysis, lack of response to induction was inversely associated with remission after escalation. Bowel frequency and >2 prior biologics were associated with time to escalation (Table 3). Conclusion UST dose escalation resulted in clinical remission in >50% of UC patients and was more effective in those with loss of response compared to no/minimal response after induction. Prospective studies are needed to identify UC subpopulations that will benefit from various dosing strategies of UST.

scholarly journals Real-world safety of palbociclib in breast cancer patients in the United States: a new user cohort study

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Daniel C. Beachler ◽  
Cynthia de Luise ◽  
Aziza Jamal-Allial ◽  
Ruihua Yin ◽  
Devon H. Taylor ◽  
...  
Keyword(s):  
Breast Cancer ◽  
United States ◽  
Pulmonary Embolism ◽  
Cohort Study ◽  
Real World ◽  
The United States ◽  
Elevated Risk ◽  
Breast Cancer Patients ◽  
Increased Risk ◽  
Serious Infections

Abstract Background There is limited real-world safety information on palbociclib for treatment of advanced stage HR+/HER2- breast cancer. Methods We conducted a cohort study of breast cancer patients initiating palbociclib and fulvestrant from February 2015 to September 2017 using the HealthCore Integrated Research Database (HIRD), a longitudinal claims database of commercial health plan members in the United States. The historical comparator cohort comprised patients initiating fulvestrant monotherapy from January 2011 to January 2015. Propensity score matching and Cox regression were used to estimate hazard ratios for various safety events. For acute liver injury (ALI), additional analyses and medical record validation were conducted. Results There were 2445 patients who initiated palbociclib including 566 new users of palbociclib-fulvestrant, and 2316 historical new users of fulvestrant monotherapy. Compared to these historical new users of fulvestrant monotherapy, new users of palbociclib-fulvestrant had a greater than 2-fold elevated risk for neutropenia, leukopenia, thrombocytopenia, stomatitis and mucositis, and ALI. Incidence of anemia and QT prolongation were more weakly associated, and incidences of serious infections and pulmonary embolism were similar between groups after propensity score matching. After adjustment for additional ALI risk factors, the elevated risk of ALI in new users of palbociclib-fulvestrant persisted (e.g. primary ALI algorithm hazard ratio (HR) = 3.0, 95% confidence interval (CI) = 1.1–8.4). Conclusions This real-world study found increased risks of several adverse events identified in clinical trials, including neutropenia, leukopenia, and thrombocytopenia, but no increased risk of serious infections or pulmonary embolism when comparing new users of palbociclib-fulvestrant to fulvestrant monotherapy. We observed an increased risk of ALI, extending clinical trial findings of significant imbalances in grade 3/4 elevations of alanine aminotransferase (ALT).

scholarly journals P461 Intolerance to 5-aminosalicylate is a risk of poor prognosis in ulcerative colitis patients

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S409-S410
Author(s):  
T Fujii ◽  
S Hibiya ◽  
C Maeyashiki ◽  
E Saito ◽  
K Takenaka ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Cohort Study ◽  
Confidence Interval ◽  
Maintenance Therapy ◽  
Retrospective Review ◽  
Poor Prognosis ◽  
Hazard Ratio ◽  
Multicenter Cohort Study ◽  
Multicenter Cohort ◽  
Significant Difference

Abstract Background 5-Aminosalicylates (5-ASA) are the key drugs in induction and maintenance therapy in ulcerative colitis (UC). Some UC patients are involved in 5-ASA intolerance after induction of oral 5-ASA compounds. There is no evidence of the prognosis including the risk of colectomy in 5-ASA intolerant UC patients. Methods The aim of this study is to establish the prognosis of 5-ASA intolerant UC patients in a multicenter cohort study. A retrospective review of a prospective multicenter database (2014–2018) of 1,574 UC patients was carried out and a total of 1,286 patients treated with oral 5-ASA compounds were enrolled. We compared the risk of colectomy and biologics induction between patients (i) tolerant to first 5-ASA compound (1079), (ii) intolerant to first 5-ASA compound but tolerant to other 5-ASA compound (107) and (iii) intolerant to 5-ASA compound and withdrawal of 5-ASA (100). Results We identified 1,286 patients with UC, of which 40 patients (3.1%) resulted in colectomy and 247 patients (19%) treated with biologics. Colectomy rate in patients (iii) intolerant to 5-ASA and withdrawal of 5-ASA were higher than (i) tolerant to first 5-ASA and (ii) intolerant to first 5-ASA but tolerant to other 5-ASA (9.0%, 2.7%, 1.9%, respectively). (iii) Patients withdrawal of 5-ASA showed higher risk of colectomy compared with (i) tolerant to first 5-ASA (Hazard ratio (HR) 4.71, 95% Confidence interval (CI): 2.04–10.8). The risk of colectomy among (ii) patients intolerant to first 5-ASA but tolerant to other 5-ASA showed no significant difference compared with (i) tolerant to first 5-ASA (HR 0.76, 95% CI: 0.43–1.35). The biologics induction rate in (iii) patients withdrawal of 5-ASA was significantly higher than (i) tolerant to first 5-ASA and (ii) intolerant to first 5-ASA but tolerant to other 5-ASA (37%, 18%, 16%, respectively). Also (iii) patients withdrawal of 5-ASA showed higher risk of induction with biologics compared with (i) tolerant to first 5-ASA (HR 2.35, 95% CI: 1.50–3.68). Those risk among (ii) patients intolerant to first 5-ASA but tolerant to other 5-ASA showed no significant difference compared with (i) tolerant to first 5-ASA (HR 0.76, 95% CI: 0.43–1.35). Conclusion Patients with UC who had 5-ASA intolerance and withdrew from 5-ASA showed poor prognosis. We should consider trying other 5-ASA compounds even if the patients had intolerance to one 5-ASA compound.

Comparison of real-world outcomes of adalimumab and infliximab for patients with ulcerative colitis in the United States

2016 ◽  
Vol 32 (7) ◽  
pp. 1233-1241 ◽  
Author(s):  
William J. Sandborn ◽  
Atsushi Sakuraba ◽  
Anthony Wang ◽  
Dendy Macaulay ◽  
William Reichmann ◽  
...  
Keyword(s):  
United States ◽  
Ulcerative Colitis ◽  
Real World ◽  
The United States

Sa1258 Comparison of Real-World Outcomes of Adalimumab (ADA) and Infliximab (IFX) for Patients With Ulcerative Colitis (UC) in the United States

2015 ◽  
Vol 148 (4) ◽  
pp. S-272 ◽  
Author(s):  
William Sandborn ◽  
Atsushi Sakuraba ◽  
A Burak Ozbay ◽  
Rachael A. Sorg ◽  
William Reichmann ◽  
...  
Keyword(s):  
United States ◽  
Ulcerative Colitis ◽  
Real World ◽  
The United States

scholarly journals Descriptive Epidemiology of Adolescent Clavicle Fractures: Results From the FACTS (Function after Adolescent Clavicle Trauma and Surgery) Prospective, Multicenter Cohort Study

2020 ◽  
Vol 8 (5) ◽  
pp. 232596712092134
Author(s):  
Henry B. Ellis ◽  
Ying Li ◽  
Donald S. Bae ◽  
Leslie A. Kalish ◽  
Philip L. Wilson ◽  
...  
Keyword(s):  
Cohort Study ◽  
Tertiary Care ◽  
The United States ◽  
Mechanism Of Injury ◽  
Descriptive Epidemiology ◽  
Multicenter Cohort Study ◽  
Multicenter Cohort ◽  
Clavicle Fractures ◽  
Operative Fixation ◽  
Direct Blow

Background: The majority of previous investigations on operative fixation of clavicle fractures have been related to the adult population, with occasional assessments of the younger, more commonly affected adolescent population. Despite limited prospective data for adolescents, the incidence of operative fixation of adolescent diaphyseal clavicle fractures has increased. Purpose: To detail the demographic features and descriptive epidemiology of a large pooled cohort of adolescent patients with diaphyseal clavicle fractures presenting to pediatric tertiary care centers in the United States through an observational, prospective, multicenter cohort study (Function after Adolescent Clavicle Trauma and Surgery [FACTS]). Study Design: Cross-sectional study; Level of evidence, 4. Methods: Patients aged 10 to 18 years who were treated for a diaphyseal clavicle fracture between August 2013 and February 2016 at 1 of 8 geographically diverse, high-volume, tertiary care pediatric centers were screened. Treatment was rendered by any of the pediatric orthopaedic providers at each of the 8 institutions, which totaled more than 50 different providers. Age, sex, race, ethnicity, fracture laterality, hand dominance, mechanism of injury, injury activity, athletic participation, fracture characteristics, and treatment decisions were prospectively recorded in those who were eligible and consented to enroll. Results: A total of 545 patients were included in the cohort. The mean age of the study population was 14.1 ± 2.1 years, and 79% were male. Fractures occurred on the nondominant side (56%) more frequently than the dominant side (44%). Sport was the predominant activity during which the injury occurred (66%), followed by horseplay (12%) and biking (6%). The primary mechanism of injury was a direct blow/hit to the shoulder (60%). Overall, 54% were completely displaced fractures, defined as fractures with no anatomic cortical contact between fragments. Mean shortening within the completely displaced group was 21.9 mm when measuring the distance between fragment ends (end to end) and 12.4 mm when measuring the distance between the fragment end to the corresponding cortical defect (cortex to corresponding cortex) on the other fragment (ie, true shortening). Comminution was present in 18% of all fractures. While 83% of all clavicle fractures were treated nonoperatively, 32% of completely displaced fractures underwent open reduction and internal fixation. Conclusion: Adolescent clavicle fractures occurred more commonly in male patients during sports, secondary to a direct blow to the shoulder, and on the nondominant side. Slightly more than half of these fractures were completely displaced, and approximately one-fifth were comminuted. Within this large cohort, approximately one-third of patients with completely displaced fractures underwent surgery, allowing for future prospective comparative analyses of radiographic, clinical, and functional outcomes.

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