Vedolizumab demonstrated significantly greater efficacy as induction and maintenance therapy for UC than placebo in patients naive to TNF antagonists and patients with TNF antagonist failure. There were numerically greater treatment differences at Week 6 among patients receiving vedolizumab who were naive to TNF antagonists than patients with TNF antagonist failure. ClinicalTrials.gov no: NCT00783718.

Vedolizumab had increased efficacy over placebo in CD patients irrespective of TNF-α antagonist treatment history. Overall, rates of response and remission were numerically higher in patients receiving vedolizumab as a first biologic than in patients who had experienced TNF failure.

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IntroductionThe efficacy and safety of vedolizumab, a gut-selective α4β7 integrin antibody, were demonstrated in the GEMINI 1 and GEMINI 2 clinical trials of adults aged 18–80 years. We investigated the efficacy and safety of vedolizumab in patients stratified by age from the GEMINI trials.MethodsSafety and efficacy, including clinical response, clinical remission, and corticosteroid-free remission, at week 6 and/or 52 were determined post hoc in patients aged <35, 35 to <55, and ≥55 years.ResultsAt baseline, 353, 412, and 130 ulcerative colitis (UC) and 582, 443, and 90 Crohn’s disease (CD) patients were aged <35, 35 to <55, and ≥55. Of these patients, 56 were aged ≥65 years (UC: 33, CD: 23). Trends favoring vedolizumab over placebo were observed for most efficacy endpoints irrespective of patient age; some variability between subgroups was observed. Safety profiles of vedolizumab and placebo were similar in all age groups. Vedolizumab-treated patients aged ≥55 had the lowest incidence of serious infections (0.9 per 100 person–years) and adverse events leading to hospitalization (14.8 per 100 person–years). There were no age-related differences in the incidence of adverse hematological events, malignancy, or death.ConclusionsThe safety and efficacy of vedolizumab in patients with UC or CD were similar for all age groups. The number of patients in the oldest age group in these analyses was small; thus further studies of vedolizumab in larger cohorts of elderly patients are warranted.FundingMillennium Pharmaceuticals, Inc. (d/b/a Takeda Pharmaceuticals International Co.).Electronic supplementary materialThe online version of this article (doi:10.1007/s12325-016-0467-6) contains supplementary material, which is available to authorized users.

Opioids are a group of analgesic agents commonly used in clinical practice. The three classical opioid receptors are MOP, DOP and KOP. The NOP (N/OFQ) receptor is considered to be a non-opioid branch of the opioid receptor family. Opioid receptors are G-protein-coupled receptors which cause cellular hyperpolarisation when bound to opioid agonists. Opioids may be classified according to their mode of synthesis into alkaloids, semi-synthetic and synthetic compounds. Opioid use disorder (OUD) is an emerging issue and important lessons can be learnt from the United States where opioid epidemic was declared as a national emergency in 2017.

A solid organ transplant is life-saving therapy that engenders the use of immunosuppressive medications for the lifetime of the transplanted organ and its recipient. Conventional therapy includes both induction therapy (a biologic that is infused peri-operatively) followed by maintenance therapy. The cost of these medications is a constant concern and the advent of generics has brought this cost down modestly. For those lacking long term insurance coverage, this may be a significant out of pocket expense that is not affordable. Moreover, transplant Centers are managing higher risk transplant recipients that require more complex induction regimens and longer term use of such biologic agents in the context of desensitization or abrogation of de novo antibody mediated injury. While in kidney transplantation, Medicare part B covers three years of medication, there is frequent non-adherence due to cost after that time-point. The impact of the Affordable Care Act remains uncertain at this time. Finally the pipeline of new therapies is limited due to the cost of development of a drug, the inherent cost of clinical studies, and lack of defined endpoints for newer therapies in high risk patients. These new therapies are of high value to the community but will contribute additional burden to current drug costs.

OBJECTIVE: To analyze the efficacy and safety of nintedanib in patients with fibrosing autoimmune disease-related interstitial lung diseases (ILDs) with a progressive phenotype. METHODS: The INBUILD trial enrolled subjects with a fibrosing ILD other than idiopathic pulmonary fibrosis, with diffuse fibrosing lung disease of >10% extent on high-resolution computed tomography, forced vital capacity (FVC) 45% predicted and diffusing capacity of the lungs for carbon monoxide 30%-<80% predicted. Subjects fulfilled protocol-defined criteria for progression of ILD within the 24 months before screening, despite management deemed appropriate in clinical practice. Subjects were randomized to receive nintedanib or placebo. We assessed the rate of decline in FVC (mL/year) and adverse events over 52 weeks in the subgroup with autoimmune disease-related ILDs. RESULTS: Among 170 subjects with autoimmune disease-related ILDs, the rate of decline in FVC over 52 weeks was -75.9 mL/year with nintedanib versus -178.6 mL/year with placebo (difference 102.7 mL/year [95% CI 23.2, 182.2]; nominal P=0.012). No heterogeneity was detected in the effect of nintedanib versus placebo across subgroups by ILD diagnosis (P=0.91). The most frequent adverse event was diarrhea, reported in 63.4% and 27.3% of subjects in the nintedanib and placebo groups, respectively. Adverse events led to permanent discontinuation of trial drug in 17.1% and 10.2% of subjects in the nintedanib and placebo groups, respectively. CONCLUSION: In the INBUILD trial, nintedanib slowed the rate of decline in FVC in subjects with progressive fibrosing autoimmune disease-related ILDs, with adverse events that were manageable for most subjects.

Multidrug resistance (MDR) has emerged as the main problem in anti-cancer therapy. Although MDR involves complex factors and processes, the main pivot is the expression of multidrug efflux pumps. P-glycoprotein (P-gp) belongs to the family of adenosine triphosphate (ATP)-binding cassette (ABC) transporters. It functions in cellular detoxification, pumping a wide range of xenobiotic compounds out of the cell. An attractive therapeutic strategy for overcoming MDR is to inhibit the transport function of P-gp and thus, increase intracellular concentration of drugs. Recently, various types of P-gp inhibitors have been found and used in experiments. However, none of them has passed clinical trials due to their high side-effects. Hence, the search for alternatives, such as plant-based P-gp inhibitors have gained attention recently. Therefore, we give an overview of the source, function, structure and mechanism of plant-based P-gp inhibitors and give more attention to cancer-related studies. These products could be the future potential drug candidates for further research as P-gp inhibitors.