Long-Term Colectomy Rate After Intensive Intravenous Corticosteroid Therapy for Ulcerative Colitis Prior to the Immunosuppressive Treatment Era

Abstract Background An episode of acute severe ulcerative colitis (UC) is a watershed event during the disease course with a heightened risk of colectomy during and following these episodes.1 The prompt identification of these events followed by the early implementation of appropriate treatment is essential to obtaining the best clinical outcomes for these unwell patients. The majority of published risk scores predicting the important clinical outcomes of intravenous corticosteroid therapy failure and colectomy-by-discharge rely on clinical data from days 1–3 of therapy.2 There is a paucity of tools that allow for a simple and individualised prediction of risk of corticosteroid therapy failure during the earliest stages of admission. Methods Data were prospectively obtained from 349 presentations of moderate–severe UC requiring hospital admission to a tertiary referral hospital. The failure of intravenous corticosteroid therapy was strictly defined by the (Oxford) Day 3 and Day 7 criteria.3 Seventeen clinical, laboratory and endoscopic variables all available within 24 h of hospital presentation were assessed for their ability to differentiate intravenous corticosteroid therapy responders from non-responders. A stepwise generalised linear model was formulated based on the results of the initial univariate analyses. Results Intravenous corticosteroid therapy failure occurred in 208/349 (60%) of presentations. The formulated risk score included the variables of oral corticosteroid therapy failure, bowel frequency and serum albumin concentration with or without the Mayo endoscopic subscore (MES). With the addition of the MES, the area under the curve (AUC) of the risk score was 0.758. When the positive predictive value of the score (threshold) for correctly predicting intravenous corticosteroid therapy failure was set at 85%, 105/275 (38%) of presentations with available data were identified as high risk for corticosteroid therapy failure (Figure 1). Conclusion This practical risk assessment tool provides clinicians with a personalised prediction of the likelihood of success of a course of intravenous corticosteroid therapy in moderate–severe UC. It enables the identification of individuals at high risk of treatment failure who may be suitable for consideration of early treatment escalation or screening for appropriate clinical trials. References

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Cytapheresis in Patients with Severe Ulcerative Colitis after Failure of Intravenous Corticosteroid: A Long-Term Retrospective Cohort Study

Gut and Liver ◽

10.5009/gnl.2009.3.1.41 ◽

2009 ◽

Vol 3 (1) ◽

pp. 41-47 ◽

Cited By ~ 2

Author(s):

Ken Fukunaga ◽

Kazuko Nagase ◽

Takeshi Kusaka ◽

Nobuyuki Hida ◽

Yoshio Ohda ◽

...

Keyword(s):

Ulcerative Colitis ◽

Cohort Study ◽

Retrospective Cohort Study ◽

Retrospective Cohort ◽

Severe Ulcerative Colitis ◽

Intravenous Corticosteroid

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3424 Serial Biomarker Monitoring Predicts Long Term Outcomes in Acute Graft Versus Host Disease

Journal of Clinical and Translational Science ◽

10.1017/cts.2019.261 ◽

2019 ◽

Vol 3 (s1) ◽

pp. 114-114

Author(s):

Hrishikesh Krishna Srinagesh ◽

Urvi Kapoor ◽

Mina Aziz ◽

Kaitlyn Ben-David ◽

...

Keyword(s):

Regression Model ◽

Clinical Response ◽

Corticosteroid Therapy ◽

Acute Gvhd ◽

Accurate Determination ◽

Immunosuppressive Treatment ◽

Response To Treatment ◽

Training Set ◽

Validation Set

OBJECTIVES/SPECIFIC AIMS: The first aim of the study is to evaluate the accuracy of serum biomarkers of acute GVHD measured after four weeks of corticosteroid therapy to predict 6 month NRM. The second aim of this study is to compare the accuracy of the biomarker algorithm to that of clinical response to corticosteroids after four weeks. The third aim of the study is to develop a novel regression model that uses weekly biomarker measurements over the first month of corticosteroid therapy to predict 6 month NRM. METHODS/STUDY POPULATION:. Patients who received HCT at one of 22 IRB-approved centers and provided blood samples to the Mount Sinai Acute GVHD International Consortium (MAGIC) biorepository and developed GVHD between January 2008 to May 2018 are included in this study. Patients were divided by time into a training set (Jan 2008-Dec 2015, n=233) for model development and a validation set (Jan 2015-May 2018, n=357) to evaluate the predictive performance of the model. The later time of the validation set was chosen deliberately to model contemporaneous GVHD treatment practices. The size of each group was designed so that there would be roughly equal numbers of deaths in both groups. RESULTS/ANTICIPATED RESULTS:. Serum concentrations of GVHD biomarkers after one month of corticosteroid therapy were measured in the validation set, and the predicted probability of NRM ($\hat{\rm p}$) was computed according to the previously published algorithm: $\log[-\log(1 - \hat{\rm p})]=-11.263 + 1.844({\rm logST}2)+ 0.577({\rm logREG}3\alpha)$. The performance of the biomarker algorithm was evaluated by creating receiver operating characteristic (ROC) curves and calculating the area under the curve (AUC) in the validation set. The AUC of the biomarker algorithm was a significantly better predictor of 6 month NRM than clinical response to treatment after four weeks of corticosteroids (0.84 vs. 0.64, p<0.001), which is a clinically relevant improvement in accuracy. To evaluate serial biomarker monitoring, serum biomarker concentrations will be measured weekly at five time points from treatment initiation to one month after corticosteroid therapy. We will use these values in the training set to develop a regression model for 6 month NRM that accounts for repeated biomarker measurements. The performance of this model will be tested in the validation set and the accuracy of the serial biomarker measurements will be compared to the accuracy of measuring biomarkers at the single time point after four weeks of corticosteroid therapy. An AUC improvement of 0.05 would be considered clinically significant. DISCUSSION/SIGNIFICANCE OF IMPACT: Clinical response to treatment after four weeks has been the standard endpoint in GVHD interventional trials for decades. If biomarkers measured at the same time more accurately predict long term mortality, this study would provide the basis for a novel endpoint in GVHD trials and enable more accurate determination of effect size of experimental interventions. An accurate biomarker algorithm will prove useful in guiding immunosuppressive treatment decisions for patients with GVHD. Patients identified by the algorithm as low-risk may benefit from reduced-dose corticosteroid therapy, potentially reducing lethal opportunistic infections. Patients identified as high-risk will be candidates for more intensive immunosuppression or investigational therapies. This precision medicine approach tailors therapy to the individual patient’s biology.

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LONG-TERM STEROID-IMMUNOSUPPRESSIVE TREATMENT OF THE CHILDHOOD NEPHROTIC SYNDROME

PEDIATRICS ◽

10.1542/peds.47.4.731 ◽

1971 ◽

Vol 47 (4) ◽

pp. 731-736

Author(s):

R. Pachioli ◽

R. Genova

Keyword(s):

Nephrotic Syndrome ◽

Corticosteroid Therapy ◽

Immunosuppressive Agents ◽

Immunosuppressive Treatment ◽

Childhood Nephrotic Syndrome ◽

Long Time

In the last 16 years at the Nephrotic Center of the Children's Clinic in Modena, 319 children have been subjected to treatment, 127 of which were subjected only to corticosteroid therapy, while 192 were subjected to corticosteroids associated with immunodepressive drugs, such as 6-mercaptopurine, azathioprine, cyclophosphamide. The associated treatment has proved to be of great value chiefly in the cortico-resistant and cortico-dependent cases, allowing a complete and lasting normalization in children who had been treated for a long time with corticosteroids, without showing any conspicuous results, but relevant secondary symptoms. Among the several immunosuppressive agents, cyclophosphamide turned out to be the most effective.

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P333 Endoscopic severity and CRP predict failure of medical rescue therapy in patients with acute severe ulcerative colitis

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab076.457 ◽

2021 ◽

Vol 15 (Supplement_1) ◽

pp. S357-S357

Author(s):

P Kakkadasam Ramaswamy ◽

D Subhaharan ◽

L Willmann ◽

J Edwards ◽

D Shukla ◽

...

Keyword(s):

Ulcerative Colitis ◽

Logistic Regression ◽

Regression Analysis ◽

Cyclosporin A ◽

Corticosteroid Therapy ◽

Disease Duration ◽

Rescue Therapy ◽

Multivariable Analysis ◽

Severe Ulcerative Colitis ◽

Intravenous Corticosteroid

Abstract Background The efficacy of Infliximab and Cyclosporin A as medical rescue therapy in patients with corticosteroid refractory acute severe ulcerative colitis (ASUC) is well established. We aimed to identify predictors of failure of medical rescue therapy and colectomy during the same admission in this population. Methods Patients hospitalized with ASUC who received infliximab or cyclosporin A after failing intravenous corticosteroid therapy between 1st January 2013 to 31stJuly, 2020 at two Australian tertiary IBD centres were retrospectively analysed. Patients who underwent colectomy during the same admission after medical rescue therapy were defined as non-responders. Logistic regression analysis was performed to identify predictors of colectomy during same admission. Results 226 episodes of ASUC [110 (48.7%) female, median disease duration 2 years] were analysed. 104 (46%) episodes required rescue therapy [94 episodes received medical rescue (16 cyclosporine/78 Infliximab) and 10 underwent direct colectomy]. In patients receiving medical rescue therapy, 16 (17%) underwent colectomy during same admission and 28 (29.8%) underwent colectomy by 12 months. On multivariable analysis, UCEIS score at admission [Coef 0.100 (0.02-0.17), p 0.011] and CRP on Day 3 post-rescue therapy [Coef 0.004 (0.0007-0.007), p 0.018] were significant for predicting colectomy during the same admission. A score with 1 point for each variable (UCEIS score ≥ 7 and CRP value of ≥ 22 mg/L on day 3 post medical rescue therapy) was developed. A score of 2 points had sensitivity 57%, specificity 97%, PPV 80%, NPV 91%, accuracy 89% for predicting colectomy during the same admission and sensitivity 33%, specificity 94%, PPV 80%, NPV 67%, accuracy 69% for predicting colectomy at 12 months. Conclusion UCEIS and CRP on day 3 after rescue therapy are predictors of non-response to medical rescue therapy and need for colectomy during the admission for the ASUC episode. Combination of UCEIS ≥ 7 and CRP ≥ 22mg/L on day 3 post medical rescue therapy has a PPV of 80% for colectomy during same admission and at 12 months. The score can be used to make decisions about colectomy or further medical rescue therapy.

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