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 acceptableIntroduction: 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 acceptabl

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

Efficacy of single and repeated administration of ketamine in unipolar and bipolar depression : a meta-analysis of randomized clinical trials

Background Due to unmet clinical needs for efficient drugs with a rapid onset of antidepressant effects, we aimed to evaluate the efficacy of single-dose ketamine in different subgroups of patients with major depression and establish whether repeated ketamine administration could be a viable strategy to maintain treatment gains. Methods Electronic databases (Medline via PubMed, Embase, Cochrane Library, Trip Database) were systematically searched until February 22, 2019, for published peer-reviewed randomized controlled trials (RCTs) concerning a single and repeated administration of ketamine in patients with major depression. All relevant RCTs were selected and critically appraised, and a meta-analysis of eligible studies was performed. Results A total of 20 studies were included in the meta-analysis. The largest effect of ketamine vs. controls in reducing depressive symptoms was observed at 24 h (SMD = - 0.89; 95% CI - 1.24; - 0.53; p < 0.00001); however, a significant difference was shown for up to 7 days after a single dose. Significant differences compared with controls were observed for up to 7 days in treatment-resistant patients and when ketamine was added to ongoing antidepressant treatment, while there were no significant differences at 7 days when ketamine was used as monotherapy. In patients with major depression, initial antidepressant effects of ketamine were maintained during repeated dosing. At 2-3 weeks of repeated ketamine treatment, significant reduction of depression severity scores was observed: SMD = - 0.70; 95% CI - 1.15; - 0.25 or SMD = - 0.81; 95% CI - 1.41; - 0.20 (depending on the dosing regimen used); p ≤ 0.009 vs placebo. Conclusions Our meta-analysis revealed rapid and robust antidepressant effects of single-dose ketamine in patients with treatment-resistant depression (TRD). By pooling data from RCTs, we showed for the first time that repeated ketamine administration is effective in sustaining initial antidepressant effects observed after single dosing

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

Forest plot of comparison: nevirapine vs 1 NNRTI (efavirenz) added to the background regimen.

<p>Forest plot of comparison: nevirapine vs 1 NNRTI (efavirenz) added to the background regimen.</p