Safety of Biologic and Small Molecule Therapy for Inflammatory Bowel Disease Among Solid Organ Transplant Recipients: Systematic Review and Meta-Analysis.

BACKGROUND: Patients undergoing organ transplantation are often on immunosuppressing medications to prevent rejection of the transplant. The data on use of concomitant immunosuppression for inflammatory bowel disease (IBD) and organ transplant management are limited. This study sought to evaluate the safety of biologic and small molecule therapy for the treatment of IBD among solid organ transplant recipients. METHODS: Medline, Embase, and Web of Science databases were systematically searched for studies reporting on safety outcomes associated with the use of biologic and small molecule therapy (infliximab, adalimumab, certolizumab, golimumab, vedolizumab, ustekinumab, and tofacitinib) in patients with IBD postsolid organ transplant (eg, liver, kidney, heart, lung, pancreas). The primary outcome was infectious complications. Secondary outcomes included serious infections, colectomy, and discontinuation of biologic therapy. RESULTS: Seven hundred ninety-seven articles were identified for screening, yielding 16 articles for the meta-analyses with information on 163 patients. Antitumor necrosis factor α (Anti-TNFs; infliximab and adalimumab) were used in 8 studies, vedolizumab in 6 studies, and a combination of ustekinumab or vedolizumab and anti-TNFs in 2 studies. Two studies reported outcomes after kidney and cardiac transplant respectively, whereas the rest of the studies included patients with liver transplants. The rates of all infections and serious infections were 20.09 per 100 person-years (100-PY; 95% CI, 12.23-32.99 per 100-PY, I2 = 54%) and 17.39 per 100-PY (95% CI, 11.73-25.78 per 100-PY, I2 = 21%), respectively. The rates of colectomy and biologic medication discontinuation were 12.62 per 100-PY (95% CI, 6.34-25.11 per 100-PY, I2 = 34%) and 19.68 per 100-PY (95% CI, 9.97-38.84 per 100-PY, I2 = 74%), respectively. No cases of venous thromboembolism or death attributable to biologic use were reported. CONCLUSION: Biologic therapy is overall well tolerated in patients with solid organ transplant. Long-term studies are needed to better define the role of specific agents in this patient population.

Colorectal Cancer Prevention in Inflammatory Bowel Disease: A Systematic Analysis of the Overall Quality of Guideline Recommendations.

BACKGROUND: Owing to the increased risk of colorectal cancer (CRC) in patients with inflammatory bowel disease (IBD), numerous societies developed preventative guidelines. We aimed to assess the overall quality of CRC prevention guidelines in IBD. METHODS: A systematic search was performed in multiple databases to identify all guidelines pertaining to CRC prevention in IBD in September 2020. All guidelines were reviewed for conflicts of interest (COIs)/funding, recommendation quality/strength, external guideline review, use of patient representation, and plans for update-as per Institute of Medicine standards. In addition, recommendations were compared amongst societies. RESULTS: One hundred forty-nine recommendations from 14 different guidelines/societies were included. Not all guidelines provided recommendations on key elements surrounding (1) screening initiation and surveillance, (2) screening modality, (3) pharmacological chemoprevention, (4) dysplasia management and follow-up, and (5) molecular marker use. Only 71% of guidelines disclosed COIs, 43% reported industry funding, 14% were externally reviewed, 7% included patient representation, and 36% had plans for update. Of the total recommendations, 7.4%, 23.5%, and 69.1% were based on high,- moderate-, and low-quality evidence, respectively. Additionally, 20.1% of recommendations were strong, 14.1%, were weak/conditional, and 65.8% did not provide a strength. The proportion of high-quality evidence (P = 0.34) and strong recommendations (P = 0.57) did not significantly differ across societies. CONCLUSIONS: Many guidelines do not provide recommendations on key aspects of CRC prevention in IBD. Over 90% of recommendations are based on low- to moderate-quality evidence; therefore, further studies on CRC prevention in IBD are needed to improve the overall quality of evidence.

Effectiveness and Safety of Tofacitinib for Ulcerative Colitis: Systematic Review and Meta-analysis.

BACKGROUND: The objective of our systematic review and meta-analysis was to evaluate the effectiveness and safety of tofacitinib in the treatment of moderate-severe ulcerative colitis (UC). METHODS: We searched Medline, Embase, Web of Science, and Cochrane Central to identify articles and abstracts reporting efficacy or safety data on tofacitinib use in UC. Primary outcome assessed was remission. Secondary outcomes included clinical response, steroid free remission, and adverse events (AEs). RESULTS: A total of 26 studies were included. The rates of remission were 29.81% [95% confidence interval (CI): 22.37%-37.25%, I2 : 90%] at week 8, 32.27% (95% CI: 27.67%-36.88%, I2 : 42%) at 6 months and 38.03% (95% CI: 33.59%-42.48%, I2 : 0%) at 1-year. Clinical response rates were 59.41% (95% CI: 55.03%-63.94%, I2 : 61%) at week 8, 48.99% (95% CI: 36.92%-61.06%, I2 : 91%) at 6 months and 50.87% (95% CI: 42.16%-59.58%, I2 : 67%) at 1-year. Odds ratio of clinical response at week 8 in biologic naive versus biologic experienced patients was 1.59 (95% CI: 0.54-4.63). Pooled incidence rate for serious infections, major adverse cardiovascular events, and nonmelanotic squamous cell malignancies across all doses was 4.41 per 100-patient years (PYs) (95% CI: 2.32-8.38 per 100-PY, I2 : 78%), 0.91 per 100-PY (95% CI: 0.43-1.93 per 100-PY, I2 : 37%) and 0.91 per 100-PY (95% CI: 0.61-1.34 per 100-PY, I2 : 0%), respectively. Higher dose was associated with an increased frequency of AEs. CONCLUSIONS: While the overall efficacy and safety of tofacitinib in moderate-severe UC is consistent with clinical trial data, the dose dependent increase in AEs highlights the significance of early dose de-escalation. Rate of clinical response after tofacitinb induction was similar in biologic naive and biologic experienced patients.

Pros and Cons of Performing Early Endoscopy in Geriatric Patients Admitted with Non-variceal Upper Gastrointestinal Bleeding: Analysis of the US National Inpatient Database.

BACKGROUND: Age greater than 65 years is a well-defined risk factor for increased mortality in patients with non-variceal upper gastrointestinal bleeding (NVGIB). Endoscopy is indicated in most patients at any age but presents unique risks in the elderly cohort, and ideal timing is unclear. This study examined the association between outcomes and early (within 24 h) esophagogastroduodenoscopy (EGD) among elderly patients with NVGIB. METHODS: All patients over age 65 admitted primarily for NVGIB who underwent EGD were included from the National Inpatient Sample 2016-2017. Clinical outcomes stratified by early EGD versus late EGD were compared after adjustment for comorbidities and bleeding severity using inverse probability of treatment weighting with survey-adjusted linear and logistic regression. RESULTS: Out of estimated 625,530 admissions with a primary diagnosis of NVGIB, 120,835 met eligibility criteria; 24,830 underwent early EGD. Mean length of stay and total charges decreased by 1.17 days (95%CI 1.04-1.30, P < 0.001) and $5717.24 (95%CI 4034.57-7399.91, P < 0.001), respectively, in the early EGD group. Early EGD increased the odds ratio of death 1.32 (95%CI 1.06-1.64, P 0.01) and transfer to other hospitals 1.48 (95%CI 1.22-1.81, P < 0.001). No change was seen in the requirement for surgery or angiography. Rates of discharge to a nursing facility or home health were similar. CONCLUSION: In a comprehensive cohort of geriatric patients with NVGIB, early EGD is associated with decreased hospital stay and charges, but also with increased mortality and inter-hospital transfer. Further research is needed to determine the optimal management of this vulnerable population.

Feature selection and predicting chemotherapy-induced ulcerative mucositis using machine learning methods.

OBJECTIVE: Ulcerative mucositis (UM) is a devastating complication of most cancer therapies with less recognized risk factors. Whilst risk predictions are most vital in adverse events, we utilized Machine learning (ML) approaches for predicting chemotherapy-induced UM. METHODS: We utilized 2017 National Inpatient Sample database to identify discharges with antineoplastic chemotherapy-induced UM among those received chemotherapy as part of their cancer treatment. We used forward selection and backward elimination for feature selection; lasso and Gradient Boosting Method were used for building our linear and non-linear models. RESULTS: In 2017, there were 253 (unweighted numbers) chemotherapy-induced UM patient discharges from 21,626 (unweighted numbers) adult patients who received antineoplastic chemotherapy as part of their cancer treatment. Our linear model, lasso showed performance (C-statistics) AUC: 0.75 (test dataset), 0.75 (training dataset); the Gradient Boosting Method (GBM) model showed AUC: 0.76 in the training and 0.79 in the test datasets. The feature selection derived from stepwise forward selection and backward elimination methods showed variables of importance--antineoplastic chemotherapy-induced pancytopenia, agranulocytosis due to cancer chemotherapy, fluid and electrolyte imbalance, age, anemia due to chemotherapy, median household income, and depression. Higher importance variable derived from GBM in the order of importance were antineoplastic chemotherapy-induced pancytopenia > co-morbidity score > agranulocytosis due to cancer chemotherapy > age > and fluid and electrolyte imbalance. Further, when the analysis was stratified to females only, the ML models performed better than the unstratified model. CONCLUSION: Our study showed ML methods performed well in predicting the chemotherapy-induced UM. Predictors identified through ML approach matched to the clinically meaningful and previously discussed predictors of the chemotherapy-induced UM.

Association between palliative care referral and burden of illness among cancers of the lip, oral cavity and pharynx.

PURPOSE: To evaluate the burden of illness--length of stay (LOS), total charges, and discharge disposition--among cancers of the lip, oral cavity and pharynx (CLOP) patients with and without palliative care (PC) referral. METHODS: This cross-sectional study utilized the 2017 National inpatient sample database to identify hospitalizations with a primary diagnosis of CLOP. Generalized linear models were used to assess the association between PC referral status and the outcomes-LOS, total charges, and discharge disposition while controlling for patients' characteristics. RESULTS: There were 4165 PC referral among 52, 524 CLOP patients. The geometric mean of LOS for non-PC referral patients was 3.7 days, and for PC referral was 5.02 days, P < 0.001. In the adjusted analysis, CLOP patients with PC referral were more likely to have a higher LOS (Coefficient:1.16; 95% CI, 1.01-1.25) compared to those without PC referral. The geometric mean of total charge among non-PC referral group was 48,308 USD, and CLOP-PC referral was 48,983 USD, P = 0.72. After adjusting for covariates, there was still no significant difference between the PC and non-PC referral groups. Discharge disposition were considerably different across the non-PC vs. PC referral groups. Compared to non-PC referral patients, PC referral patients were more likely to be discharge to skilled nursing facility, intermediate care, and another type of facility (aOR = 7.10; CIs, 5.51-9.12), or home health care (aOR = 4.13; CIs, 3.31-5.15). CONCLUSION: During primary hospitalization, total charges was not different between patient non-PC and PC referral groups; however, the LOS and discharge dispositions were significantly different.

Meta-analysis of Virtual-based Chromoendoscopy Compared With Dye-spraying Chromoendoscopy Standard and High-definition White Light Endoscopy in Patients With Inflammatory Bowel Disease at Increased Risk of Colon Cancer.

BACKGROUND: Patients with inflammatory bowel disease (IBD) have an increased risk of colorectal cancer. We sought to assess the comparative efficacy of virtual chromoendoscopy (VCE) vs high definition white light endoscopy (HDWLE) or dye-spraying chromoendoscopy (DCE) through a meta-analysis and rating the quality of evidence. METHODS: A systematic review of the literature was performed through February 15, 2019. Primary outcomes were number of patients in whom dysplasia was identified and number of dysplastic lesions identified in these patients. We included only randomized control trials (RCTs) and performed meta-analysis using RevMan5.3. RESULTS: Of the 3205 studies identified, 11 RCTs were included, with a total of 1328 patients. Per patient analysis, VCE was not statistically different compared with DCE (risk ratio [RR] 0.77; 95% CI, 0.55-1.08) or HDWLE (RR 0.72; 95% CI, 0.45-1.15). However, per dysplasia analysis, VCE was not statistically different compared with DCE (RR 0.72; 95% CI, 0.47-1.11) and inferior compared with HDWLE (RR 0.62; 95% CI, 0.44-0.88). The quality of evidence was moderate in the HDWLE and low to moderate in the DCE studies. CONCLUSION: Based on this meta-analysis, VCE was as good as HDWLE and DCE in identifying dysplasia per patient analysis. However, per dysplasia analysis, VCE was inferior compared with HDWLE and no different from DCE. Further studies need to examine the efficacy of each individual VCE technique.

Is Therapeutic Drug Monitoring for Anti-tumour Necrosis Factor Agents in Adults With Inflammatory Bowel Disease Ready for Standard of Care? A Systematic Review and Meta-analysis.

INTRODUCTION: Using therapeutic drug monitoring [TDM] in adult patients with inflammatory bowel disease [IBD] remains controversial. We conducted a systematic review and meta-analysis to answer four clinical PICO [Population, Intervention, Comparator, Outcome] questions. METHODS: We searched MEDLINE, Embase, Web of Science, and Cochrane Central from inception to June 30, 2019. Remission was defined by the manuscripts' definitions of clinical remission. Data were analysed using RevMan 5.3. Quality of evidence was assessed with GRADE methodology. RESULTS: We identified and screened 3365 abstracts and 11 articles. PICO 1 Reactive vs No TDM: six studies pooled showed 57.1% [257/450] failed to achieve remission following reactive TDM vs 44.7% [268/600] in the no TDM group (risk ratio [RR]: 1.14; 95% confidence interval [CI] 0.88-1.47). PICO 2 Proactive vs no TDM: five studies pooled showed 19.5% [75/384] failed to maintain remission in the proactive TDM group vs 33.4% [248/742] in the no TDM group [RR: 0.60; 95% CI 0.35-1.04]. PICO 3 Proactive vs Reactive TDM: two retrospective studies pooled showed 14.2% [26/183] failure to maintain remission in the proactive TDM group and 64.7% [119/184] in the reactive TDM group [RR: 0.22; 95% CI 0.15-0.32]. PICO 4 TDM [proactive/reactive] vs No TDM: we pooled 10 studies showing 39.7% [332/837] failed to achieve remission in the TDM [proactive/reactive] cohort vs 40.3% [428/1063] in the no TDM cohort [RR: 0.94; 95% CI 0.77-1.14]. Overall, the quality of evidence in each PICO was very low when using GRADE. CONCLUSIONS: This meta-analysis shows that data supporting use of TDM in adults are limited and of very low quality. Further well-designed randomized controlled trials are needed to determine the place of TDM in clinical practice.