Burden of hidradenitis suppurativa: a systematic literature review of patient reported outcomes

Introduction Hidradenitis suppurativa (HS) has a profound negative impact on patients’ health-related quality of life (HRQoL). Here we summarize the evidence on HRQoL and Patient Reported Outcomes (PROs) in patients with HS in real-world settings by conducting a systematic literature review (SLR) of observational studies. Methods Data sources included MEDLINE, Embase & PsycINFO between January 1, 2010 and August 29, 2021, and conference proceedings between 2019 and 2021. Identified abstracts were reviewed and screened independently by two reviewers. Eligibility criteria included patients with HS of any severity, sample size ≥ 100, reporting PROs including HRQoL measures. Included studies were critically appraised. Results Fifty-eight observational studies matched inclusion criteria. Dermatology Life Quality Index (DLQI) was the most commonly utilized instrument: 57% of included studies reported mean baseline DLQI scores, ranging between 8.4 and 16.9, indicating a very large impact on the patients’ HRQoL. Higher scores were reported with increasing disease severity and among female patients. Pain was assessed mostly by an 11-point (0–10) numeric rating scale (NRS) with a mean baseline score ranging from 3.6 to 7.7 indicating moderate to high pain levels. There was a negative impact of HS on patients’ psychological well-being, based on PRO scores related to depression and anxiety. A high proportion of sexual dysfunction was reported, with a larger impact on women than men. Work productivity and leisure activity were consistently found to be impaired in patients with HS. Conclusions All included studies reported a negative impact of HS on patients’ lives. A diverse set of disease- and non-disease-specific PRO instruments were utilized highlighting the need for more consistent use of HS-specific validated PRO instruments to assess the impact of HS on the different aspects of patients’ HRQoL to allow for data to be more meaningfully interpreted and compared in real-world settings. Patients with HS need better disease management approaches that address the observed low quality of life

The efficacy and tolerability of perampanel and other recently approved anti-epileptic drugs for the treatment of refractory partial onset seizure: a systematic review and Bayesian network meta-analysis.

OBJECTIVES: This paper compares the efficacy and tolerability of perampanel (PER) relative to other recently approved anti-epileptic drug (AEDs) - lacosamide (LCS), retigabine (RTG), and eslicarbazepine (ESL) for the adjunctive treatment of partial onset seizures with or without secondary generalization and specifically in the secondary generalization subgroup. MATERIALS AND METHODS: A systematic literature review of all RCTs of PER and selected AEDs in EMBASE, Medline, and the Cochrane Central from 1998 to January 2011 with an update in PubMed in March 2013 was performed. A network meta-analysis was conducted for 50% responder rate for overall seizures; withdrawal due to adverse events; seizure freedom; and 50% responder rate for secondary generalized seizures. RESULTS: Twelve RCTs (three PER, three LCS, three RTG and three ESL) were included. PER performed significantly better than placebo for 'responder rate' (OR 2.151, 95% CrI 1.348-3.472) and 'seizure freedom' (OR 2.507, 95% CrI 1.067-7.429). When compared to other agents, PER was found to be equally effective. For 'withdrawal due to adverse events', PER had the lowest odds ratio vs. placebo compared with other AEDs. In the analysis for the subgroup of patients with secondary generalization, only four RCTs (three PER and one LCS) met the inclusion criteria for one outcome (responder rate) for LCS. In this subgroup, PER was statistically significantly better than placebo (OR 2.448, 95% CrI 1.088-5.828). CONCLUSION: PER was statistically significantly superior to placebo in responder rate, seizure freedom, and responder rate in the secondary generalization population. Though PER had statistically significant greater withdrawal compared to placebo, it had the lowest ORs vs. placebo, suggesting a superior safety profile among the comparators included in this analysis. In patients with partial onset seizure with secondary generalization, PER had a statistically significant effect on responder rate compared to placebo

A network meta-analysis of immunotherapy-based treatments for advanced nonsquamous non-small cell lung cancer

Introduction: In the absence of head-to-head trials comparing immunotherapies for advanced nonsquamous non-small-cell lung cancer (NsqNSCLC), a network meta-analysis (NMA) was conducted to compare the relative efficacy of these treatments. Materials & methods: A systematic literature review of randomized controlled trials evaluating first-line-to-progression and second-line treatments for advanced NsqNSCLC informed Bayesian NMAs for overall survival (OS) and progression-free survival (PFS) end points. Results: Among first-line-to-progression treatments, pembrolizumab + pemetrexed + platinum showed the greatest OS benefit versus other regimens and a PFS benefit versus all but three regimens. Among second-line treatments, an OS benefit was seen for atezolizumab, nivolumab and pembrolizumab versus docetaxel. Conclusion: Pembrolizumab + pemetrexed + platinum showed the maximum OS benefit in the first-line setting. In the second-line setting, anti-PD-1/anti-PD-L1 monotherapies were better than docetaxel

Systematic review and network meta-analysis of the efficacy and safety of tumour necrosis factor inhibitor-methotrexate combination therapy versus triple therapy in rheumatoid arthritis

Clinical trials have not consistently demonstrated differences between tumour necrosis factor inhibitor (TNFi) plus methotrexate and triple therapy (methotrexate plus hydroxychloroquine plus sulfasalazine) in rheumatoid arthritis (RA). The study objective was to estimate the efficacy, radiographic benefits, safety and patient-reported outcomes of TNFi-methotrexate versus triple therapy in patients with RA. A systematic review and network meta-analysis (NMA) of randomised controlled trials of TNFi-methotrexate or triple therapy as one of the treatment arms in patients with an inadequate response to or who were naive to methotrexate was conducted. American College of Rheumatology 70% response criteria (ACR70) at 6 months was the prespecified primary endpoint to evaluate depth of response. Data from direct and indirect comparisons between TNFi-methotrexate and triple therapy were pooled and quantitatively analysed using fixed-effects and random-effects Bayesian models. We analysed 33 studies in patients with inadequate response to methotrexate and 19 in patients naive to methotrexate. In inadequate responders, triple therapy was associated with lower odds of achieving ACR70 at 6 months compared with TNFi-methotrexate (OR 0.35, 95% credible interval (CrI) 0.19 to 0.64). Most secondary endpoints tended to favour TNFi-methotrexate in terms of OR direction; however, no clear increased likelihood of achieving these endpoints was observed for either therapy. The odds of infection were lower with triple therapy than with TNFi-methotrexate (OR 0.08, 95% CrI 0.00 to 0.57). There were no differences observed between the two regimens in patients naive to methotrexate. In this NMA, triple therapy was associated with 65% lower odds of achieving ACR70 at 6 months compared with TNFi-methotrexate in patients with inadequate response to methotrexate. Although secondary endpoints numerically favoured TNFi-methotrexate, no clear differences were observed. The odds of infection were greater with TNFi-methotrexate. No differences were observed for patients naive to methotrexate. These results may help inform care of patients who fail methotrexate first-line therap

Association Between CHADS2 Risk Factors and Anticoagulation-Related Bleeding: A Systematic Literature Review

OBJECTIVE: To determine the strength of evidence supporting an accentuated bleeding risk when patients with CHADS2 risk factors (chronic heart failure, hypertension, advanced age, diabetes, and prior stroke/transient ischemic attack) receive warfarin