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.

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

BACKGROUND AND AIM: The aim of this systematic review was to evaluate the efficacy and safety of biological agents (vedolizumab, abatacept, visilizumab, golimumab) in patients with active moderate to severe ulcerative colitis. METHODS: This paper was prepared according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The systematic literature search was performed in PubMed, Embase, Cochrane Library, and other databases until December 27, 2013 to identify randomized controlled trials fulfilling the established inclusion criteria for this review. RESULTS: Eight randomized controlled trials were included in the systematic review. Vedolizumab was significantly more effective compared with placebo (P < 0.05) increasing the percentage of patients with a clinical response, clinical remission and mucosal healing in the induction phase, and patients with a clinical remission and mucosal healing in the maintenance phase. Similarly, golimumab was significantly more effective than placebo (P < 0.05) regarding the percentage of patients with a clinical response and mucosal healing in the induction phase, and patients with a clinical response, clinical remission, and mucosal healing in the maintenance phase. The safety of these two biological agents was comparable with placebo during the treatment (P > 0.05). However, the efficacy of visilizumab or abatacept was related to the higher risk of treatment failure and a worse safety profile than placebo. CONCLUSIONS: The results of the systematic review demonstrated that the efficacy and safety of particular biological agents are differentiated. Vedolizumab and golimumab occurred more effective, and comparably as safe as placebo in patients with active moderate to severe ulcerative colitis increasing the number of available therapeutic options.

The effectiveness of dimethyl fumarate monotherapy in the treatment of relapsing-remitting multiple sclerosis: a systematic review and meta-analysis.

BACKGROUND: Dimethyl fumarate (BG-12, Tecfidera®) is a new oral drug approved by FDA and EMA in March 2013 for relapsing - remitting multiple sclerosis (RRMS). The drug was much anticipated because of its possible superiority over currently available medications: fingolimod and teriflunomide as the only MS treatments currently available in oral form. OBJECTIVE: The aim of this systematic review with meta-analysis was to assess the efficacy and safety of BG-12 in the treatment of RRMS. METHODS: A systematic literature search was conducted in Medline/PubMed, EMBASE, and Cochrane Library up till 3(rd) November, 2013. We sought all published randomized clinical trials evaluating the use of dimethyl fumarate for the treatment of patients with RRMS. All included studies were critically appraised and analyzed with the use of Review Manager 5.1.0. software according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement protocol. RESULTS: Two trials, DEFINE and CONFIRM involved 2 651 patients and compared dimethyl fumarate taken either two or three times daily with placebo in patients with RRMS. Additionally in CONFIRM trial third group of patients received glatiramer acetate. The overall results of the meta-analysis showed that BG-12 (at both dosages) given to patients with RRMS is safe and statistically significantly more effective than placebo in reducing the proportion of patients who had a relapse by 2 years, the rate of disability progression and the mean number of gadolinium-enhancing lesions at 2 years. The comparison between BG-12 and glatiramer acetate revealed that the analyzed agent could potentially be more effective in the treatment of RRMS. CONCLUSIONS: Despite limited RCTs data available, both analyzed BG-12 regimens showed their efficacy on clinical disease parameters and other measures of disease activity in RRMS. The safety profile of the study agent was acceptable.

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.

Nevirapine-based regimens in HIV-infected antiretroviral-naive patients: systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Nevirapine belongs to the group of non-nucleoside reverse transcriptase inhibitors (NNRTIs) and is commonly administered in first-line treatment of HIV infection. OBJECTIVE: Systematic review and meta-analysis was undertaken to compare effectiveness of nevirapine-based regimens with other antiretroviral schedules used as an initial treatment of HIV-infected antiretroviral-naive subjects. METHODS: Electronic databases (PubMed, EMBASE, the Cochrane Library, Trip Database) were searched up to 28 December 2012 for randomized controlled trials (RCTs) published as a full text and regarding nevirapine-based regimens used as a initial treatment for HIV infection. Meta-analysis was performed with RevMan(®) V 5.2 software. RESULTS: Twelve RCTs were included in the systematic review and all of them were suitable for meta-analysis. Results of the meta-analysis have shown that nevirapine, efavirenz, and ritonavir-boosted protease inhibitor, added to the background regimens, were equally effective in terms of reaching undetectable plasma HIV RNA level as well as risk of disease progression or death. Compared with ritonavir-boosted protease inhibitor-based regimens, nevirapine-based regimens statistically significantly increased the risk of discontinuation of assigned treatment (RR=3.10; 95% CI: 1.14-8.41; p<0.05). CONCLUSIONS: Despite limited RCTs data available for particular comparisons, our results suggest that nevirapine-based regimens may be considered for first-line treatment of HIV-infected adults, due to their comparable efficacy to the other currently recommended initial antiretroviral therapies.

The effectiveness of tofacitinib, a novel Janus kinase inhibitor, in the treatment of rheumatoid arthritis: a systematic review and meta-analysis.

The aim of the present study was to conduct a meta-analysis of the effectiveness of tofacitinib, a novel oral Janus kinase inhibitor, recently approved for the treatment of active rheumatoid arthritis in patients who have failed previous treatment with methotrexate (MTX) or other disease-modifying antirheumatic drugs (DMARDs). A systematic literature search was conducted in PubMed, EMBASE, Cochrane Library, and other databases till 3 May 2013. All included studies were analyzed with the use of the Review Manager 5.1.0. software according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement protocol. Nine randomized controlled trials (RCTs) comparing tofacitinib with placebo were identified. Two of them additionally provided the comparison with adalimumab. However, only eight RCTs met the inclusion criteria for the meta-analysis. The overall results of the meta-analysis showed that tofacitinib provided a statistically significant improvement according to the response criteria (ACR20/50/70) after 12 weeks of treatment when compared to placebo (p < 0.00001). Moreover, it was demonstrated that tofacitinib was significantly superior to adalimumab in achieving the ACR50 response criteria at week 12 (p = 0.003). For the safety analysis, there were no statistically significant differences between tofacitinib-, adalimumab-, and placebo-treated patients in respect to the risk of serious adverse events or treatment discontinuation due to adverse reactions (p > 0.05). The findings of this systematic review with meta-analysis indicate that tofacitinib monotherapy or with background methotrexate provides early statistically significant and clinically important improvement in rheumatoid arthritis symptoms and has an acceptable safety profile comparable to that of placebo. The results of the present meta-analysis show that the frequency of serious adverse events was not increased after tofacitinib treatment. In addition, tofacitinib might provide an effective treatment option compared to intravenous or subcutaneous biological DMARDs, as suggested by the result of the comparison made regarding tofacitinib vs. adalimumab ACR50 response rate.

Tumor necrosis factor-α antibodies (infliximab, adalimumab and certolizumab) in Crohn's disease: systematic review and meta-analysis.

INTRODUCTION: This meta-analysis compares the effectiveness and safety of tumor necrosis factor α (TNF-α) antibodies (infliximab, adalimumab and certolizumab) with either a placebo or each of them in the treatment of Crohn's disease (CD). MATERIAL AND METHODS: A systematic review of literature published up to November 2012 was performed and a meta-analysis of identified studies was carried out. We searched the following databases: PubMed, EMBASE, The Cochrane Library and others. Only randomized or clinical controlled trials were included. RESULTS: Nineteen clinical trials fulfilled the established criteria (5 studies for infliximab vs. placebo, 6 for each adalimumab or certolizumab vs. placebo and 2 comparing infliximab with adalimumab). The results of meta-analysis showed that anti-TNF therapy in patients with CD is safe and statistically significantly more effective when compared with the placebo for induction of remission at week 4 (RB = 1.90, 95% CI: 1.55-2.33, p < 0.00001), maintenance of remission at weeks 20-30 (RB = 1.86, 95% CI: 1.61-2.15, p < 0.00001) and at weeks 48-56 (RB = 2.75, 95% CI: 2.13-3.54, p < 0.00001) in patients who responded to the induction therapy and patients randomized before the induction. Anti-TNF agents were also superior to the placebo in fistula healing (during short-term induction, as well as long-term maintenance) and inducing CR-70 but not CR-100 at week 4. Moreover, the anti-TNF therapy had a significant effect on achieving both CR-70 and CR-100 during long-term maintenance. CONCLUSIONS: Infliximab, adalimumab and certolizumab are effective as both induction and maintenance therapy in moderate to severe Crohn's disease in adults, including patients with fistulas. The safety profile was acceptable.