Indirect Treatment Comparisons of Lenacapavir Plus Optimized Background Regimen Versus Other Treatments for Multidrug-Resistant Human Immunodeficiency Virus

Background/AimsHeavily treatment-experienced (HTE) people with human immunodeficiency virus (HIV) (PWH) may not achieve virologic suppression (VS) with combination antiretroviral therapy due to multidrug resistance (MDR), intolerance, and safety concerns. These PWH often receive highly individualized treatment regimens, but these regimens may not enable PWH to achieve VS, thereby halting disease progression. Novel medications are required for treating individuals with MDR HIV. Lenacapavir (LEN), a first-in-class HIV capsid inhibitor, is under investigation for the treatment of HTE individuals with MDR HIV in the phase 2/3 CAPELLA study. This study aimed to compare LEN plus optimized background regimen (OBR) with fostemsavir (FTR) + OBR, ibalizumab (IBA) + OBR, and OBR alone in terms of VS, CD4 cell count change from baseline, immunologic recovery, and discontinuation due to adverse events, using indirect treatment comparisons.MethodsA systematic review identified clinical evidence on HIV-1 treatments in HTE PWH. A feasibility assessment evaluated the identified studies for indirect treatment comparison analyses based on population characteristics, interventions, comparators, and outcomes of interest. Unanchored simulated treatment comparisons of LEN + OBR versus comparators were conducted.ResultsLEN + OBR had 6.57 times higher odds of VS at weeks 24 to 28 than FTR + OBR (95% confidence interval [CI] 1.34-32.28), 8.93 times higher odds of VS than IBA + OBR (95% CI 2.07-38.46), and 12.74 times higher odds of VS than OBR alone (95% CI 1.70-95.37). Change from baseline in CD4 cell count was similar across LEN + OBR, FTR + OBR, and IBA + OBR.ConclusionLEN + OBR has statistically significantly greater odds of VS at weeks 24 to 28 than its comparators and represents a novel treatment for people with MDR HIV.     

Evaluating Matching‐Adjusted Indirect Comparisons in Practice: A Case Study of Patients with Attention‐Deficit/Hyperactivity Disorder

Differences in patient characteristics across trials may bias efficacy estimates from indirect treatment comparisons. To address this issue, matching‐adjusted indirect comparison (MAIC) measures treatment efficacy after weighting individual patient data to match patient characteristics across trials. To date, however, there is no consensus on how best to implement MAIC. To address this issue, we applied MAIC to measure how two attention‐deficit/hyperactivity disorder (ADHD) treatments (guanfacine extended release and atomoxetine hydrochloride) affect patients' ADHD symptoms, as measured by the ADHD Rating Scale IV score. We tested MAIC sensitivity to: matched patient characteristics, matched statistical moments, weighting matrix, and placebo‐arm matching (i.e., matching on outcomes in the placebo arm). After applying MAIC, guanfacine and atomoxetine had similar reductions in ADHD symptoms (Δ: 0.4, p < 0.737). The results were similar for three of four sensitivity analyses. When we applied MAIC with placebo‐arm matching, however, guanfacine reduced symptoms more than atomoxetine (Δ: ?3.9, p < 0.004). We discuss the implication of this finding and advise MAIC practitioners to carefully consider the use of placebo‐arm matching, depending on the presence of residual confounding across trials. Copyright © 2016 John Wiley & Sons, Ltd.