Introduction Clinical studies have revealed that fixed-dose combinations (FDCs) of drugs can have a better effect on blood pressure than free-equivalent combinations (FECs). Our objectives were to perform an up-to-date assessment of the effectiveness of FDCs and FECs in antihypertensive...

To assess the comparative effectiveness and safety of novel biologic therapies in psoriatic arthritis (PsA) and to establish the position of the non-anti-tumor necrosis factor α (TNF-α) biologic drugs in the treatment regimen of the disease. A systematic review and network meta-analysis (NMA) was conducted according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) requirements. Two investigators identified the studies, abstracted data, and assessed the risk of bias independently. The NMA was conducted for efficacy [American College of Rheumatology (ACR) criteria, ACR20 and ACR50; psoriasis area and severity index (PASI), PASI75] and safety outcomes [any adverse events (AEs) and serious adverse events (SAEs)]; treatments were ranked using the P score for each outcome. The PROSPERO registration number was 42017072200. MEDLINE/PubMed, Embase, Cochrane Library, and ClinicalTrials.gov were searched from the inception of each database to July 10, 2017. Randomized controlled trials (RCTs) for abatacept, apremilast, secukinumab or ustekinumab in adults with moderate and severe PsA were included. The overall PsA population and anti-TNF-α-naive, anti-TNF-α-failure, or anti-TNF-α-experienced subpopulations were considered. We identified eight eligible RCTs and included them in the systematic review and NMA. Significant differences in ACR20 response rate were revealed between secukinumab 150 mg and apremilast 20 mg [relative risk; RR = 2.55 (CI—confidence interval; 1.24, 5.23)] and between secukinumab 300 mg and apremilast 20 or 30 mg [RR = 3.57 CI (1.48, 8.64) and RR = 2.84 CI (1.18, 6.86), respectively]. Any AEs occurred more often in apremilast 20 and 30 mg compared with placebo [RR = 0.58 CI (0.45, 0.74) and RR = 0.58 CI (0.45, 0.75), respectively] but also compared with secukinumab 150 mg [RR = 0.54 CI (0.35, 0.81) and RR = 0.45 CI (0.35, 0.82), respectively]. No significant differences were revealed for SAEs among biologics and between biologics and placebo. In the overall population, as well as in the anti-TNF-α-naive subpopulation, secukinumab at a dose of 300 and 150 mg was ranked the highest for the ACR20 endpoint, while in the anti-TNF-α-experienced subpopulation, secukinumab 300 mg and apremilast 30 mg revealed the highest rank. Secukinumab 75 mg was the safest drug in terms of any AEs, but for SEAs the safest was ustekinumab 90 mg. Our study revealed no significant differences among non-anti-TNF-α biologics in the treatment of PsA in the comparisons performed with regards to the highest efficacy and safety. Both in the overall population and in the analyzed subpopulations, secukinumab 300 mg was ranked the highest for the ACR20 response rate. Secukinumab 300 mg was the safest drug in terms of any AEs, and ustekinumab 90 mg presented the lowest overall risk of SAEs. Head-to-head trials and evaluation of comparative efficacy and safety between non-TNF-α biologics are warranted to inform clinical decision making with a relevant treatment paradigm.

Introduction : Sipuleucel-T is a novel active cellular immunotherapy for the treatment of asymptomatic or minimally symptomatic metastatic castrate-resistant prostate cancer (mCRPC). It is assumed to be associated with less adverse events than conventional docetaxel-based chemotherapy....

Evidence on indirect cost of Crohn’s disease (CD) is available but typically provides information on the loss of productivity at paid work of patients. In the present study, the quality of life and indirect costs of CD patients were assessed (overall and by disease severity). A self-report questionnaire-based study among adult Polish patients with CD was performed. We collected data on patients’ characteristics, quality of life, loss of productivity, consumption of medical resources, and out-of-pocket expenses. The disease severity was determined using the patient’s version of the Harvey-Bradshaw index. Productivity costs were assessed from the social perspective, using a human capital approach. The cost of absenteeism, presenteeism and permanent work disability was valuated using the gross domestic product per worker. The patients’ productivity loss at unpaid work was measured by time inputs of others to assist patients. The productivity loss among informal caregivers and patients’ productivity loss at unpaid work were valuated with the average wage in Poland. The results were adjusted for confounders. The responses from 200 patients (47% in remission) were analysed. The mean utility index was 0.839 (SD 0.171). The total indirect cost was estimated at €462.47 per patient per month (24.0%, absenteeism; 35.0%, work disability; 30.4%, presenteeism; 0.4%, productivity loss at unpaid work; and 10.4%, informal care). A significant correlation of the quality of life and productivity losses with disease severity was observed. Compared with active disease, the remission subgroup had a higher utility index by 16% (p<0.001) and lower indirect costs by 71% (p = 0.003) for absenteeism, 41% (p = 0.030) for presenteeism, 76% (p<0.001) for productivity loss at unpaid work, and 75% (p<0.001) for informal care. Our study revealed the social burden of CD and high dependency of indirect costs and quality of life on the severity of CD in Poland.

Within the concentration range of 1-20 μM, orthovanadate (Na₃ VO₄) demonstrated a time and dose-dependent inhibition of autocrine growth of the human carcinoma cell lines A549 (lung), HTB44 (kidney) and DU145 (prostate), as compared to appropriate controls (without Na₃ VO₄). The investigation was conducted by two methods: staining with N-hexa-methylpararosaniline (crystal violet=CV) or bromide3-(4,5-dimethyltio-azo-2)-2,5-diphenyl-tetrazole (MTT). In 5, 10 and 20 μM of Na₃ VO₄ in serum-free medium, the mean values of these two tests for A549 were approximately 40%, 45% or 65% as compared to the appropriate controls. HTB44 had the greatest opportunity (statistically insignificant) at lower vanadium concentrations (up to 10 μM), whereas at 20 μM growth inhibition of these cells was approximately 50% of the controls. DU145 showed approximately 33%, 65% and 98% growth inhibition for 5, 10 and 20 μM of Na₃ VO₄, respectively Additionally, hypothetical curves obtained by a MANOVA test based on the CV results after 72 h incubation with Na₃ VO₄ in serum-free medium, and an example of a time-dependent effect of Na₃ VO₄ on A549 cells, were also presented. Sodium orthovanadate was also examined for its cytotoxic capabilities, especially its ability to induce tumor cell apoptosis; the results were compared with the effect of paclitaxel. The target cells were dyed by differential staining (HOECHST33258 and propidium iodide) after 3 h and 24 h (DU145) or 3 h and 72 h (A549) of incubation with the vanadium compound. Contrary to the two cancer cell lines (viable, apoptotic or necrotic in experimental conditions), the renal HTB44 cells were insensitive up to 15 μM Na₃ VO₄ concentrations. After 3 h incubation with Na₃ VO₄, both lung (A549) and prostate (DU145) cancer cells showed a slight but significant reduction in the percentage of viable cells, and an increased amount of apoptotic cells. In contrast to the lung cells, DU145 prostate cells after 24 h were more sensitive to paclitaxel than to sodium orthovanadate. In the case of lung cells, the time of incubation was prolonged (to 72 h) to allow for a study of the effect of orthovanadate in greater detail. After 72 h of incubation with Na₃ VO₄ or paclitaxel, A549 showed a similar level of viable cells (25-32% of total cultured cells); however, the percentage of apoptotic cells was higher in the case of A549 cells – ca 36% for both drugs, but the concentration of Na₃ VO₄ was significantly greater than paclitaxel levels.

The objective is to examine the cost-utility of sipuleucel-T immunotherapy in asymptomatic or minimally symptomatic castration-resistant prostate cancer patients. The addition of sipuleucel-T immunotherapy to standard treatment led to a gain of 0.37 quality-adjusted life-year (QALY) at an additional cost of US$104,536. The incremental cost-utility ratio was US$283,000 per QALY saved. Threshold sensitivity analyses indicated that a price reduction of at least 53%, or application in a group of patients resulting in the relative reduction in the mortality rate of at least 39%, ought to augment the economic value of this regimen. Sipuleucel-T immunotherapy treatment at the current price with 96.5% certainty is not cost-effective. The specific group of patients who will benefit more from the treatment should be revealed and treated, or the cost of the vaccine should be lowered significantly to increase its economic value. Accounting for crossover treatment in control patients improves sipuleucel-T's value (US$132,000 per QALY saved) although further investigation is necessary.