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.

Impact of Cirrhosis on Outcomes in Inflammatory Bowel Disease Hospitalizations.

BACKGROUND: Evidence regarding outcomes in inflammatory bowel disease (IBD) hospitalizations with coexisting cirrhosis is scant. We queried the National Inpatient Sample (NIS) database to evaluate the impact of cirrhosis on hospitalization characteristics and outcomes in patients with Crohn's disease and ulcerative colitis. METHODS: All admissions that listed IBD as a primary diagnosis by ICD-10-CM code (K50.X for Crohn's disease and K51.X for ulcerative colitis) in the NIS for 2016 and 2017 were included. Attributes of admissions with cirrhosis (K74.XX, 70.3, 78.81, and 71.7) were compared with noncirrhosis IBD admissions. The primary outcome was inpatient mortality. Length of stay and total hospital charges comprised secondary outcomes. RESULTS: A total weighted sample of 276,430 IBD admissions were identified, including 4615 with a concomitant diagnosis of cirrhosis. In a multivariate model, after adjusting for comorbidities, age, alimentary surgery during the admission and hospital type (teaching, urban nonteaching or rural), the presence of cirrhosis was associated with a higher inpatient mortality [odds ratio: 1.57; 95% confidence interval (CI): 1.16-2.15] and increased cost of admission (mean difference $11,651; 95% CI: 3830-19,472). No difference was noted in length of stay (difference: 0.44 d; 95% CI: -0.12-1.02) among these groups. Among admission diagnoses, infectious complications were the primary cause of death in 93.3% (95% CI: 87.1%-99.5%) of all inpatient mortality in the IBD with cirrhosis cohort as compared with 80.1% (95% CI: 77.6%-82.7%) of the mortality among IBD patients without cirrhosis ( P =0.01). CONCLUSIONS: This study demonstrates that the presence of cirrhosis has an independent negative impact on outcomes for hospitalized patients with IBD as reflected by increased in-hospital mortality and higher cost of admission. A majority of the mortality was attributable to infections.

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.

Coccidioidomycosis masquerading as malignancy.

Skeletal coccidioidomycosis is extremely rare and in the non-endemic areas, diagnosis is often delayed or missed resulting in extensive and unnecessary medical investigation for other diseases. The authors report a case of disseminated skeletal coccidioidomycosis in a previously healthy person living in a non-endemic area, who was initially thought to have a malignancy. Due to the presence of multiple expansile lytic bone lesions on x-rays and CT scan, an extensive investigation for malignancy was done. Diagnosis of coccidioidomycosis was made when H&E and Gomori's methenamine silver staining of a bone biopsy sample revealed multiple fungal spherules, which were confirmed to be Coccidioides immitis by culture and PCR. On questioning, the patient admitted to have spent 2 weeks in Arizona (an endemic area) few months ago. He was discharged home on long-term fluconazole. At 1 month clinical follow-up, a significant improvement in his lesions was noticed.