Background: Cumulative clinical improvement and speed of improvement are important to psoriasis patients.Objective: Compare cumulative benefits of biologics over 12 to 16 weeks in the treatment of moderate to severe psoriasis.Methods: A systematic literature review identified phase III trial data on Psoriasis Area and Severity Index (PASI) responses for biologics during 12 and 16 weeks of treatment. Cumulative clinical benefit, measured by the area under the curve for PASI $75% improvement (PASI 75), $90% improvement (PASI 90), and 100% improvement (PASI 100), was compared using the network meta-analysis and Bayesian methodology on the relative probability of achieving percentage of maximum area under the curve.Results: Among biologics approved for psoriasis treatment, antieinterleukin-17 biologics demonstrated consistently greater cumulative clinical benefits on PASI 75, PASI 90, and PASI 100 over the 12-or 16-week period than antieinterleukin-23 and other biologics. For biologics with 12-week data, ixekizumab and brodalumab showed greater cumulative benefits for PASI 75, PASI 90, and PASI 100 than secukinumab, followed by guselkumab, infliximab, adalimumab, ustekinumab, and etanercept. Ixekizumab showed greater cumulative benefits than all other biologics reporting 16-week data.

Pruritus appears to be an important mediator of the association between improvements in disease severity and HRQOL in patients with moderate-to-severe psoriasis.

ObjectivesOnce-daily (qd) antiretroviral therapies improve convenience and adherence. If found to be effective, nevirapine extended release (NVP XR) will confer this benefit. The TRANxITION trial examined the efficacy and safety of switching virologically suppressed patients from NVP immediate release (NVP IR) 200 mg twice daily to NVP XR 400 mg qd. MethodsAn open-label, parallel-group, noninferiority, randomized (2:1 NVP XR:NVP IR) study was performed. Adult HIV-1-infected patients receiving NVP IR plus a fixed-dose nucleoside reverse transcriptase inhibitor (NRTI) combination of lamivudine (3TC)/abacavir (ABC), tenofovir (TDF)/emtricitabine (FTC) or 3TC/zidovudine (ZDV) with undetectable viral load (VL) were enrolled in the study. The primary endpoint was continued virological suppression with VL < 50 HIV-1 RNA copies/mL up to week 24 (calculated using a time to loss of virological response algorithm). Cochran's statistic (background regimen adjusted) was used to test noninferiority. Adverse events (AEs) were recorded. ResultsAmong 443 randomized patients, continued virological suppression was observed in 93.6% (276 of 295) of NVP XR-and 92.6% (137 of 148) of NVP IR-treated patients, an observed difference of 1% [95% confidence interval (CI) -4.3, 6.0] at 24 weeks of follow-up. Noninferiority (adjusted margin of -10%) of NVP XR to NVP IR was robust and further supported by SNAPSHOT analysis. Division of Acquired Immunodeficiency Syndrome (DAIDS) grade 3 and 4 events were similar for the NVP XR and NVP IR groups (3.7 vs. 4.1%, respectively), although overall AEs were higher in the NVP XR group (75.6 vs. 60.1% for the NVP-IR group). ConclusionsNVP XR administered once daily resulted in continued virological suppression at week 24 that was noninferior to that provided by NVP IR, with similar rates of moderate and severe AEs. The higher frequency of overall AEs with NVP XR may be a consequence of the open-label design.

Introduction: High-quality randomised controlled trials (RCTs) provide the most reliable evidence on the comparative efficacy of new medicines. However, non-randomised studies (NRS) are increasingly recognised as a source of insights into the real-world performance of novel therapeutic products, particularly when traditional RCTs are impractical or lack generalisability. This means there is a growing need for synthesising evidence from RCTs and NRS in healthcare decision making, particularly given recent developments such as innovative study designs, digital technologies and linked databases across countries. Crucially, however, no formal framework exists to guide the integration of these data types. Objectives and Methods: To address this gap, we used a mixed methods approach (review of existing guidance, methodological papers, Delphi survey) to develop guidance for researchers and healthcare decision-makers on when and how to best combine evidence from NRS and RCTs to improve transparency and build confidence in the resulting summary effect estimates. Results: Our framework comprises seven steps on guiding the integration and interpretation of evidence from NRS and RCTs and we offer recommendations on the most appropriate statistical approaches based on three main analytical scenarios in healthcare decision making (specifically, ‘high-bar evidence’ when RCTs are the preferred source of evidence, ‘medium,’ and ‘low’ when NRS is the main source of inference). Conclusion: Our framework augments existing guidance on assessing the quality of NRS and their compatibility with RCTs for evidence synthesis, while also highlighting potential challenges in implementing it. This manuscript received endorsement from the International Society for Pharmacoepidemiology.

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