Paweł Kawalec

Effectiveness of targeted therapy in patients with previously untreated metastatic breast cancer: a systematic review and meta-analysis.

Breast cancer is the most common cancer and the most frequent cause of death in women. Targeted therapies offer a possibility of effective and individualized therapy based on the molecular profile of the tumor. The aim of this systematic review was to evaluate the efficacy and safety of targeted agents added to chemotherapy or endocrine therapy in patients with previously untreated metastatic breast cancer (MBC) depending on their human epidermal growth factor receptor 2 (HER2) and hormone receptor (HR) status (positive or negative). The systematic literature search was performed in PubMed, EMBASE, and the Cochrane Library to identify randomized controlled trials (RCTs). Thirteen trials were included. The addition of trastuzumab, pertuzumab, bevacizumab, or lapatinib to chemotherapy significantly (P < .05) improved objective response rate (ORR), time to failure (TTF), and overall survival (OS) in patients with HER2-positive (HER2(+)) disease. Trastuzumab or lapatinib combined with endocrine therapy significantly (P < .05) improved ORR, time to progression (TTP), and progression-free survival (PFS) in patients with HER2(+) and HR(+) disease. In patients with HER2-negative (HER2(-)) cancer, bevacizumab or lapatinib added to chemotherapy significantly (P < .05), improved ORR but did not prolong PFS and OS (P > .05). In patients with HER2(-) and HR(-) disease, trastuzumab combined with chemotherapy did not significantly improve (P > .05) ORR or PFS. Targeted therapies also increased the overall risk of adverse events. So far, there is a lack of published results for everolimus and trastuzumab emtansine trials in patients with previously untreated MBC. The addition of targeted therapy to chemotherapy or endocrine therapy using HER2 and HR status significantly improved ORR, PFS, and OS in patients with previously untreated MBC.

The safety of dipeptidyl peptidase-4 (DPP-4) inhibitors or sodium-glucose cotransporter 2 (SGLT-2) inhibitors added to metformin background therapy in patients with type 2 diabetes mellitus: a systematic review and meta-analysis.

The aim of the present meta‐analysis was to assess the safety profile of dipeptidyl peptidase‐4 (DPP‐4) inhibitors and sodium‐glucose cotransporter 2 (SGLT‐2) inhibitors in comparison with placebo as add‐on to metformin therapy in patients with type 2 diabetes. Randomized controlled trials and controlled clinical trials were identified by searching Pubmed, Embase and the Cochrane Central Register of Controlled Trials database until 15 July 2013. All included studies were critically appraised and analysed with the use of Review Manager 5.1.0 software according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses statement protocol. Twenty randomized and double‐blinded studies published in 22 articles fulfilled the inclusion criteria for meta‐analysis. The overall results demonstrated that the use of oral antidiabetic agents (analysed separately and together) was not associated with any significantly increased risk of any serious adverse events including hypoglycaemia and gastrointestinal disorders. Moreover, the use of DPP‐4 or SGLT‐2 inhibitors significantly decreased risk of diarrhoea compared with placebo, when given concomitantly with metformin. However, we found that the SGLT‐2 inhibitors were more likely to cause a genital infection. Despite some limitations, the findings of this meta‐analysis indicate that DPP‐4 or SGLT‐2 inhibitors have favourable safety profile, and such therapy, when combined with metformin is well tolerated. Copyright

The indirect costs of psoriatic arthritis: systematic review and meta-analysis

The aim of this systematic review is to collect all current data on the indirect costs (IC) related to psoriatic arthritis (PsA). The search was conducted using MEDLINE (via PubMed), Embase and Centre for Reviews and Dissemination databases. We considered original studies, systematic reviews, economic evaluations, conference abstracts and posters. All collected data were recalculated to average annual cost per patient, expressed using the consumer price index for 2013 and converted to US dollars using purchasing power parity. Eight of the identified publications presented IC of PsA. Average annual IC per patient calculated using the friction cost approach range from US

Pricing and Reimbursement of Biosimilars in Central and Eastern European Countries

1693.83 to

Safety profile of biologic drugs in the therapy of Crohn disease: A systematic review and network meta-analysis

12,318.45, while using the human capital approach they range from US

Relating Health Technology Assessment recommendations and reimbursement decisions in Poland in years 2012–2014, a retrospective analysis

1750.68 to

The indirect costs of multiple sclerosis: systematic review and meta-analysis

50,270.52. Result of the meta-analysis was a basis for calculating cost of work disability equaled US

Systematic review of the effectiveness of biological therapy for active moderate to severe ulcerative colitis

10,754.04 per patient per year in 2013 prices. This systematic review revealed a great economic burden of the disease to the society. A small number of studies on IC in PsA justify further investigations.

Implementation of the 2011 Reimbursement Act in Poland: Desired and undesired effects of the changes in reimbursement policy

Objectives: The aim of this study was to review the requirements for the reimbursement of biosimilars and to compare the reimbursement status, market share, and reimbursement costs of biosimilars in selected Central and Eastern European (CEE) countries. Methods: A questionnaire-based survey was conducted between November 2016 and January 2017 among experts from the following CEE countries: Bulgaria, Czech Republic, Croatia, Estonia, Hungary, Latvia, Lithuania, Poland, Slovakia, and Romania. The requirements for the pricing and reimbursement of biosimilars were reviewed for each country. Data on the extent of reimbursement of biologic drugs (separately for original products and biosimilars) in the years 2014 and 2015 were also collected for each country, along with data on the total pharmaceutical and total public health care budgets. Results: Our survey revealed that no specific criteria were applied for the pricing and reimbursement of biosimilars in the selected CEE countries; the price of biosimilars was usually reduced compared with original drugs and specific price discounts were common. Substitution and interchangeability were generally allowed, although in most countries they were at the discretion of the physician after a clinical assessment. Original biologic drugs and the corresponding biosimilars were usually in the same homogeneous group, and internal reference pricing was usually employed. The reimbursement rate of biosimilars in the majority of the countries was the same and amounted to 100%. Generally, the higher shares of expenditures were shown for the reimbursement of original drugs than for biosimilars, except for filgrastim, somatropin, and epoetin (alfa and zeta). The shares of expenditures on the reimbursement of biosimilar products ranged from 8.0% in Estonia in 2014 to 32.4% in Lithuania in 2015, and generally increased in 2015. The share of expenditures on reimbursement of biosimilars in the total pharmaceutical budget differed between the countries, with the highest observed value for Slovakia and Hungary and the lowest—for Croatia. Conclusions: The requirements for the pricing and reimbursement of biosimilar products as well as the access of patients to biologic treatment do not differ significantly between the considered CEE countries. Biosimilar drugs significantly influence the reimbursement systems of these countries, and the expenditure on the reimbursement of biosimilars is increasing as they are becoming more accessible to patients.

Efficacy and safety of ustekinumab in the induction therapy of TNF-α-refractory Crohn's disease patients: a systematic review and meta-analysis

BACKGROUND Crohn disease (CD) is an inflammatory bowel disease which occurs especially in developed countries of Western Europe and North America. The aim of the study was to compare the safety profile of biologic drugs in patients with CD. METHODOLOGY A systematic literature search was performed using PubMed, Embase, and CENTRAL databases, until April 27, 2016. We included randomized controlled trials (RCTs) that compared the safety of biologic drugs (infliximab, adalimumab, vedolizumab, certolizumab pegol, and ustekinumab) with one another or with placebo in patients with CD. The network meta-analysis (NMA) was conducted for an induction phase (6-10 weeks) and maintenance phase (52-56 weeks) with a Bayesian hierarchical random effects model in the ADDIS® software. The PROSPERO registration number was CRD42016032606. RESULTS Ten RCTs were included in the systematic review with NMA. In the case of the induction phase, the NMA could be conducted for the assessment of the relative safety profile of adalimumab, vedolizumab, certolizumab pegol, and ustekinumab, and in the case of the maintenance phase-of infliximab, adalimumab, and vedolizumab. There were no significant differences in the rate of adverse events in patients treated with biologics. Statistical analysis revealed that vedolizumab had the greatest probability of being the safest treatment in most endpoints in the induction phase and adalimumab-in the maintenance phase. CONCLUSIONS No significant differences between the biologics in the relative safety profile analysis were observed. Further studies are needed to confirm our findings, including head-to-head comparisons between the analyzed biologics.