Evidence for external beam radiotherapy in mediastinal Hodgkin and non-Hodgkin lymphoma - systematic review.

INTRODUCTION AND OBJECTIVE: Proton beam therapy (PBT) provides the opportunity for a more localized delivery of high energy protons and may reduce the damage to healthy tissues and vital organs. The aim of this review was to assess the effects of proton therapy for patients diagnosed with Hodgkin or non-Hodgkin lymphoma treated with mediastinal irradiation. REVIEW METHODS: A systematic search of EMBASE, MEDLINE via OVID and Cochrane Library was conducted in May 2022 according to PRISMA guidelines to identify relevant data on the efficacy and toxicity of proton beam therapy for patients diagnosed with Hodgkin or non-Hodgkin lymphoma. BRIEF DESCRIPTION OF THE STATE OF KNOWLEDGE: Of 566 screened abstracts (430 after de-duplication) 11 studies with a total of 529 patients were included. All studies were case series published between 2011-2021. Median range of follow-up time was 15-63.6 months. The overall survival (OS) for 2 years varied from 91% - 98% for 5 of the included studies. Three of the included studies had favourable outcomes with 2-year progression-free survival (PFS) ranging from 73% - 94%. Skin reaction, oesophagitis and fatigue were found to be the most common grade 1 and grade 2 toxicities. No acute or late grade 4 and higher toxicities/adverse events were observed. SUMMARY: There are data indicating that PBT may to be an effective treatment against mediastinal Hodgkin and non-Hodgkin lymphoma. Because all the studies were case series, the authors of this review have little confidence in the evidence. There remains a need for well-designed randomized controlled trials to inform about the optimal approach to proton irradiation in HL and NHL.

The Potential of Scopolamine as an Antidepressant in Major Depressive Disorder: A Systematic Review of Randomized Controlled Trials.

Major depressive disorder is one of the most severe mental disorders. It strongly impairs daily functioning, and, in extreme cases, it can lead to suicide. Although different treatment options are available for patients with depression, there is an ongoing search for novel therapeutic agents, such as scopolamine (also known as hyoscine), that would offer higher efficacy, a more rapid onset of action, and a more favorable safety profile. The aim of our study was to review the current clinical evidence regarding the use of scopolamine, a promising therapeutic option in the treatment of depression. A systematic literature search was performed using PubMed, Embase, and CENTRAL databases up to 5 June 2023. We included randomized placebo-controlled or head-to-head clinical trials that compared the clinical efficacy and safety of scopolamine in the treatment of major depressive disorder. Two reviewers independently conducted the search and study selection and rated the risk of bias for each study. Four randomized controlled trials were identified in the systematic review. The included studies investigated the use of scopolamine administered as an oral, intramuscular, or intravenous drug, alone or in combination with other antidepressants. The results indicated that scopolamine exerts antidepressant effects of varying intensity. We show that not all studies confirmed a statistically and clinically significant reduction of depressive symptoms vs. placebo. A broader perspective on scopolamine use in antidepressant treatment should be confirmed in subsequent large randomized controlled trials assessing both effectiveness and safety. Therefore, studies directly comparing the effectiveness of scopolamine depending on the route of administration are required.

An indirect comparison of ustekinumab and vedolizumab in the therapy of TNF-failure Crohn's disease patients.

AIM: An indirect comparison of ustekinumab versus vedolizumab in patients with active moderate-to-severe Crohn's disease who were nonresponsive or intolerant to previous TNF-antagonist therapy. METHODS: A systematic review was performed in Medline via PubMed, Embase, Cochrane Library, until 30 April 2017. Inclusion criteria were: randomized controlled trials, patients treated for Crohn's disease, ustekinumab or vedolizumab therapy. Included trials were critically appraised and afterward indirect comparison by Bucher was conducted; the manuscript was prepared in accordance to the PRISMA requirements. RESULTS: Five randomized controlled trials were included and assessed for homogeneity; they occurred eligible for indirect comparison referring to induction or maintenance phase of TNF-antagonist failure population treatment; no statistically significant differences in clinical response (relative benefit [RB]: 1.14; 95% CI: 0.65-1.99; p = 0.64) as well as in clinical remission (RB: 1.16; 95% CI: 0.54-2.48; p = 0.71) in induction phase of therapy were revealed; no significant disparity was presented in a maintenance phase in clinical remission (RB: 0.72; 95% CI: 0.30-1.68; p = 0.44). No significant differences were also revealed in primary and secondary nonresponders subpopulations in clinical response. Indirect comparison of the safety profile presented no statistically significant difference between the biologics (relative risk [RR]: 0.93; 95% CI: 0.81-1.08; p = 0.35). CONCLUSION: No significant differences between vedolizumab and ustekinumab in clinical response and clinical remission for induction and remission in maintenance phase of TNF refractory patients therapy were revealed. In addition, no significant disparities in the risk of adverse events suggest a similar safety profile.

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

AIM: The aim of the systematic review and meta-analysis was to assess the efficacy and safety of ustekinumab in the induction therapy of anti-TNF-α failure patients with Crohn's disease. METHODS: A systematic literature search was conducted in Medline (PubMed), EMBASE, Cochrane Library until 30 December 2016. We included randomized controlled trials that compared efficacy (clinical response and remission) and safety profile of ustekinumab in TNF-α failure Crohn's disease patients; primary and secondary TNF-α nonresponders or intolerant patients were also assessed. Included studies were critically appraised according to the PRISMA statement protocol; data aggregation with a RevMan® software was performed. RESULTS: Three randomized controlled trials were revealed in the systematic review but only two of them (CERTIFI and UNITI-1) were homogenous to be included in the meta-analysis; aggregation of data only for induction phase of therapy was possible. Clinical response was significantly higher for patients who received ustekinumab compared with placebo patients in a group of TNF-α antagonist failure patients (relative benefit [RB] = 1.62; 95% CI: 1.28-2.04) and in the following subgroups: secondary nonresponders (RB = 1.98; 95% CI: 1.49-2.63), intolerant patients (RB = 1.47; 95% CI: 1.01-2.13) and patients who failed at least two TNF-α antagonists (RB = 2.19; 95% CI: 1.53-3.14) but in case of primary nonresponders it occurred insignificant (RB = 1.22; 95% CI: 0.76-1.98). The clinical remission in TNF-α antagonist failure population was significantly higher for patients who received ustekinumab compared with placebo (RB = 1.72; 95% CI: 1.17-2.53). Pooled analysis revealed that risk of adverse events in induction phase of therapy was not significantly different (risk ratio = 0.96; 95% CI: 0.86-1.06) between ustekinumab and placebo groups. CONCLUSION: The clinical response was significantly higher for TNF-α antagonist failure patients who received ustekinumab as well as in subgroups of secondary nonresponders or intolerant patients but not in case of primary nonresponders. Ustekinumab occurred as safe as placebo in the induction as well as in a maintenance phase of therapy.

Safety Profile of Biologic Drugs in the Treatment of Inflammatory Bowel Diseases: A Systematic Review and Network Meta-analysis of Randomized Controlled Trials.

BACKGROUND AND OBJECTIVES: Biologic drugs are used in innovative therapies for the management of inflammatory bowel diseases (IBDs). The aim of this study was to compare the safety profile of biologic drugs in patients with IBD. METHODS: A systematic literature search was performed using PubMed, Embase, and CENTRAL databases, up to 22 August 2016. We included randomized, placebo-controlled, or head-to-head clinical trials that compared the safety of different biologics in patients with IBDs. Two reviewers independently conducted the search and selection of studies and rated each trial's risk of bias. The network meta-analysis (NMA) was conducted for a mid-term (20-30 weeks) and long-term (≥52 weeks) follow-up with a Bayesian hierarchical random effects model using the ADDIS® software. The PROSPERO registration number was CRD42015029884. RESULTS: Sixteen randomized controlled trials were included in the systematic review with NMA. In the case of the mid-term follow-up, it was possible to conduct the NMA for assessing the relative safety profile of certolizumab pegol and infliximab, and in the case of the long-term follow-up, of infliximab, adalimumab, golimumab, and vedolizumab. There were no significant differences in the rate of adverse events in patients treated with all analyzed biologic drugs for IBD. The analysis of probability for being the safest treatment showed that infliximab was the best option in most analyzed endpoints both in mid-term and in long-term follow-ups. CONCLUSIONS: We showed no significant differences in the relative safety profile of the analyzed biologic drugs. Further studies are needed to confirm our findings, including head-to-head comparisons between these drugs.

Effectiveness and safety of vedolizumab for treatment of Crohn's disease: a systematic review and meta-analysis.

INTRODUCTION: The aim of this systematic review (SR) and meta-analysis was to assess the efficacy and safety of vedolizumab in the treatment of Crohn's disease (CD). MATERIAL AND METHODS: A systematic literature search was conducted in Medline/PubMed, Embase and Cochrane Library until 25 January, 2015. Included studies were critically appraised according to the PRISMA protocol. Assessment in specified subgroups of CD patients and meta-analysis with Revman software were performed. RESULTS: Two randomized controlled trial (RCTs) were included in a meta-analysis for the induction phase of therapy: GEMINI II and GEMINI III. The clinical response was significantly higher for patients who received vedolizumab compared to placebo in the general population (risk benefit (RB) = 1.48; p = 0.0006) and in both analyzed subgroups: patients with previous failure of anti-TNFs treatment (RB = 1.51; p = 0.006) and patients naive to earlier anti-TNFs (RB = 1.41; p = 0.001). The clinical remission in the general population and subpopulation of TNF-antagonist naive patients was significantly higher for patients who received vedolizumab compared to placebo (RB = 1.77; p = 0.003; RB = 2.29; p = 0.0004; respectively). Meta-analysis for adverse events, serious adverse events (SAEs) and serious infections, revealed that vedolizumab was as safe as placebo in the induction phase of therapy. CONCLUSIONS: The clinical response was significantly higher for patients who received vedolizumab in the general population and in both analyzed subgroups of patients. The clinical remission in the general population and subpopulation of TNF-antagonist naive patients was significantly higher for vedolizumab, but no significant differences were revealed in the subgroup of patients with previous TNF antagonist failure.

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

Safety Profile of Biologic Drugs in the Therapy of Ulcerative Colitis: A Systematic Review and Network Meta-Analysis.

OBJECTIVES: We compared the safety profile of biologic drugs in patients with moderately to severely active ulcerative colitis (UC). METHODS: A systematic literature search was performed using Medline (PubMed), Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases through February 9, 2016. We included randomized controlled trials (RCTs) that compared the safety of biologic drugs (infliximab, adalimumab, golimumab, and vedolizumab) with one another or with placebo in patients with UC. Two reviewers independently conducted the search and selection of studies and rated the risk of bias in each trial. The network meta-analysis (NMA) was conducted for an induction phase (6-8 weeks) and maintenance phase (52-54 weeks) with a Bayesian hierarchical random effects model in Aggregate Data Drug Information System (ADDIS) software. The PROSPERO registration number was CRD42016032607. RESULTS: Seven 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, golimumab, and vedolizumab, and in the case of the maintenance phase of infliximab, adalimumab, golimumab, and vedolizumab. The methodological quality of the included RCTs was evaluated as low risk of bias, but high risk of bias in the case of attrition bias (incomplete outcome data) according to the Cochrane criteria. No significant differences were found in the rate of adverse events in patients treated with the reviewed biologics. Vedolizumab was most likely to have the most favorable safety profile in the induction phase as was infliximab for the maintenance phase. CONCLUSIONS: The assessment of the relative safety profile revealed no significant differences between the biologic drugs. Further studies are needed to confirm our findings including head-to-head comparisons between the analyzed biologics.

Vedolizumab Compared with Certolizumab in the Therapy of Crohn Disease: A Systematic Review and Indirect Comparison.

OBJECTIVES: The increasing prevalence of Crohn disease (CD) underscores the need to identify new effective drugs, which is particularly important for patients who do not respond or do not tolerate standard biologic therapies. The purpose of this analysis was to compare the efficacy and safety of vedolizumab and certolizumab pegol in patients with active moderate to severe CD. METHODS: This analysis was prepared according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A systematic literature search of Medline (PubMed), Embase, and the Cochrane Library was conducted through March 5, 2016. Studies included were randomized controlled trials (RCTs) that enrolled patients treated for CD with vedolizumab or certolizumab pegol. All studies were critically appraised; indirect comparison was performed with the Bucher method. RESULTS: Eight RCTs were identified, and four were homogeneous enough to be included in the indirect comparison of the induction phase of treatment. No statistically significant differences were found in clinical response (relative risk [RR] 1.23, 95% confidence interval [CI] 0.81-1.88) or remission (RR 1.35, 95% CI 0.89-2.07) between vedolizumab and certolizumab pegol in the overall population. Similar nonstatistically significant differences in response and remission were noted in a subgroup analysis of anti-tumor necrosis factor-naive patients (RR 1.10, 95% CI 0.72-1.66 and RR 1.98, 95% CI 0.95-4.11, respectively). In addition, there were no statistically significant differences in safety profiles. CONCLUSIONS: This indirect comparison analysis demonstrated no statistically significant differences in efficacy and safety between vedolizumab and certolizumab pegol.

Indirect costs of absenteeism due to rheumatoid arthritis, psoriasis, multiple sclerosis, insulin-dependent diabetes mellitus, and ulcerative colitis in 2012: a study based on real-life data from the Social Insurance Institution in Poland.

INTRODUCTION: The aim of this study is to assess the indirect costs of six major autoimmune diseases including seropositive rheumatoid arthritis, other types of rheumatoid arthritis, psoriasis, multiple sclerosis, Type 1 diabetes, and ulcerative colitis. METHODS: Relevant data for 2012 on sick leave and short- and long-term work disabilities were obtained from the Social Insurance Institution in Poland. Indirect costs were estimated using the human capital approach based on gross domestic product per capita, gross value added per worker, and gross income per worker in Poland in 2012 and expressed in euro. RESULTS: We recorded data on the total number of 45,500 patients. The total indirect costs were EUR 146,862,569; 353,683,508; and 108,154,271, calculated using gross domestic product, gross value added, and gross income, respectively. CONCLUSIONS: Considering only data on absenteeism collected by the Social Insurance Institution in Poland, we can conclude that the selected autoimmune diseases are associated with great indirect costs.

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

The aim of this systematic review is to collect and summarize all current data on the indirect costs related to absenteeism and presenteeism associated with multiple sclerosis. Searches were conducted using Medline, Embase and Centre for Reviews and Dissemination databases. All collected costs were recalculated to average annual cost per patient, expressed in 2014 prices US$ using the consumer price index and purchasing power parity (scenario 1) and expressed as proportion of specific gross domestic product in current local currency unit to adjust for country's development (scenario 2). Identified studies were then analyzed in order to assess their possible inclusion in the meta-analysis. The authors identified 63 records, of which 23 were eligible for meta-analysis. Overall indirect cost per patient calculated in scenario 1 was as high as US$20,167 with US$22,197 in Europe, US$17,382 in North America and US$153 in Asia. Overall indirect cost per patient calculated in scenario 2 was equal to US$16,939, with US$19,612 in Europe, US$11,592 in North America and US$899 in Asia. Overall indirect costs varied from US$3726 for patients with EDSS score less than 3 to US$19,264 for patients with Expanded Disability Status Scale score grater that 7. This review revealed the great economic burden of multiple sclerosis on society. The authors observed a great variety of the considered components of indirect costs and their definitions. Costs were higher for Europe than for other continents and were also higher for patients with a higher Expanded Disability Status Scale score.