Therapeutic drug monitoring in inflammatory bowel disease: A practical approach.

The global burden of inflammatory bowel diseases (IBD) is estimated at 4.9 million and the global prevalence exceeds 0.3%. Multiple newer therapeutic agents have broadened the options for the therapy of IBD in the last three decades. Thiopurines, however, have retained their place as maintenance therapy in IBD, especially in resource-constrained setting. But thiopurines have narrow therapeutic range, often needing discontinuation due to side effects or lack of efficacy. Biologic agents revolutionized the treatment of IBD, but the efficacy is lost in 50% of patient after one year. These outcomes are often due to inadequate drug concentrations that may lead to the development of antibodies as well as pharmacodynamic failure. Therapeutic drug monitoring (TDM) was proposed to reduce loss of response and to optimize the therapy in patients on thiopurine and biologic therapy. TDM is based on exposure-response relationship, suggesting a positive correlation between elevated serum anti-TNF concentrations and favorable therapeutic outcomes. TDM has multiple facets. This article discusses the benefits, evidence and limitations of TDM. The practical use of TDM in clinical practice is highlighted. Newer developments in the field and their relevance in practice are discussed.

Tofacitinib use in ulcerative colitis: An expert consensus for day-to-day clinical practice.

Rising number of inflammatory bowel disease (IBD) cases in developing countries necessitate clear guidance for clinicians for the appropriate use of advanced therapies. An expert consensus document was generated to guide the usage of tofacitinib, a Janus kinase inhibitor, in ulcerative colitis. Tofacitinib is a useful agent for the induction and maintenance of remission in ulcerative colitis. It can be used in the setting of biological failure or even steroid-dependent and thiopurine refractory disease. Typically, the induction dose is 10 mg BD orally. Usually, clinical response is evident within eight weeks of therapy. In those with clinical response, the dose can be reduced from 10 mg BD to 5 mg BD. Tofacitinib should be avoided or used cautiously in the elderly, patients with cardiovascular co-morbidity, uncontrolled cardiac risk factors, previous thrombotic episodes and those at high risk for venous thrombosis or previous malignancy. Baseline evaluation should include testing for and management of hepatitis B infection and latent tuberculosis. Where feasible, it is prudent to ensure complete adult vaccination, including Herpes zoster, before starting tofacitinib. The use of tofacitinib may be associated with an increased risk of infections such as herpes zoster and tuberculosis reactivation. Maternal exposure to tofacitinib should be avoided during pre-conception, pregnancy, and lactation. There is emerging evidence of tofacitinib in acute severe colitis, although the exact positioning (first-line with steroids or second-line) is uncertain.

Renal dysfunction in routine proton-pump inhibitor use may be linked to comorbidities: A real-world observational study.

INTRODUCTION: The use of proton-pump inhibitors (PPI) is linked with infrequent but serious adverse events, including acute kidney injury, chronic kidney disease (CKD) and progression of CKD. Data on renal safety in routine use of PPI are more relevant to clinical practice. We studied whether such use of PPI is associated with renal dysfunction. METHODS: Patients taking PPI for at least six weeks had serum creatinine tested pre (n = 200) and post (n = 180) recruitment. These patients were then advised to follow-up: those taking PPI for at least 90 days in the next six months (n = 77) and at least another 90 days in the following six months (n = 50), had serum creatinine tested at such follow-up. Renal dysfunction was defined as any increase in serum creatinine level above baseline. RESULTS: The 200 patients recruited had mean age 39.6 (SD 9.2) years. Ninety-eight (49%) patients had a history of previous PPI use (median six months; interquartile range [IQR] 3-24). Only 20 (11.1%) patients at six weeks, 11 (14.3%) at six months and six (12%) at one year had increase in creatinine level; a majority of them had less than 0.3 mg/dL increase. Ten of these 20 (six weeks), five of 11 (six months) and five of six (one year) had other risk factors for renal dysfunction. No patient developed CKD during the study period. CONCLUSIONS: Mild and non-progressive increase in serum creatinine occurred in 10% to 15% of patients on routine PPI use. A majority of them had other risk factors. Small sample size and short follow-up duration are a few limitations of this study.