Jinlin Song

Categorizing natural history trajectories of ambulatory function measured by the 6-minute walk distance in patients with Duchenne muscular dystrophy

Highlights • This paper shows that DMD boys could be grouped into classes sharing trajectories.• Using analysis accounting for trajectory classes, the variation was strongly reduced.• Reducing unexplained variation could help to improve DMD clinical trial design.

Daclatasvir and Sofosbuvir Versus Sofosbuvir and Ribavirin in Patients with Chronic Hepatitis C Coinfected with HIV: A Matching-adjusted Indirect Comparison

PURPOSE Our aim was to compare the efficacy and tolerability of daclatasvir plus sofosbuvir (DCV+SOF) versus SOF plus ribavirin (SOF+R) in patients coinfected with HIV and hepatitis C virus (HCV). METHODS A systematic literature review of Phase III clinical trials identified 2 trials of SOF+R-PHOTON-1 (A Phase 3, Open-Label Study to Investigate the Efficacy and Safety of GS-7977 Plus Ribavirin in Chronic Genotype 1, 2 and 3 Hepatitis C Virus [HCV] and Human Immunodeficiency Virus [HIV] Co-Infected Subjects) and PHOTON-2 (A Phase 3, Open-Label Study to Investigate the Efficacy and Safety of Sofosbuvir Plus Ribavirin in Chronic Genotype 1, 2, 3 and 4 Hepatitis C Virus [HCV] and Human Immunodeficiency Virus [HIV] Co-Infected Subjects) suitable for comparison with the trial of DCV+SOF in patients coinfected with HIV and HCV-ALLY-2 (A Phase 3 Evaluation of Daclatasvir Plus Sofosbuvir in Treatment-naïve and Treatment-experienced Chronic Hepatitis C [Genotype 1, 2, 3, 4, 5, or 6] Subjects Coinfected With Human Immunodeficiency Virus [HIV]). Individual patient data from ALLY-2 were available; published summary data were extracted and pooled for the PHOTON trials. To adjust for cross-trial differences, ALLY-2 patients were subject to the inclusion and exclusion criteria reported in the PHOTON trials and were weighted to match all available summary baseline characteristics reported in both PHOTON trials. Sustained virologic response at week 12 post-treatment (SVR12) discontinuation due to adverse events (AEs) and rates of AEs were compared. FINDINGS The SVR12 rate was significantly higher among patients treated with DCV+SOF (n = 91) than among those treated with SOF+R (n = 455) both before (96.7% vs 84.6%; P = 0.002) and after (99.9% vs 84.6%; P < 0.001) adjusting for baseline characteristics. After adjustment, compared with patients treated with SOF+R, patients receiving DCV+SOF had a significantly lower rate of discontinuation due to AEs and significantly lower rates of the following specific AEs: cough, diarrhea, insomnia, nasopharyngitis, upper respiratory tract infection, and hemoglobin <10 g/dL. IMPLICATIONS After adjustment for cross-trial differences in baseline characteristics, DCV+SOF was associated with a significantly higher SVR12 rate and lower rate of discontinuation due to AEs than SOF+R in patients coinfected with HIV and HCV.

Real‐world medication persistence with single versus multiple tablet regimens for HIV‐1 treatment

Adherence to antiretroviral (ARV) treatment for HIV‐1 is crucial to achieving optimal clinical outcomes. Simplification of regimens with once‐daily single‐tablet regimens (STRs) can improve adherence compared to multi‐tablet regimens (MTRs). This study compared real‐world persistence (a proxy for treatment effectiveness and adherence) between HIV‐1 infected patients receiving STRs versus MTRs.

Individualized Prediction of Changes in 6-Minute Walk Distance for Patients with Duchenne Muscular Dystrophy

Background Deficits in ambulatory function progress at heterogeneous rates among individuals with Duchenne muscular dystrophy (DMD). The resulting inherent variability in ambulatory outcomes has complicated the design of drug efficacy trials and clouded the interpretation of trial results. We developed a prediction model for 1-year change in the six minute walk distance (6MWD) among DMD patients, and compared its predictive value to that of commonly used prognostic factors (age, baseline 6MWD, and steroid use). Methods Natural history data were collected from DMD patients at routine follow up visits approximately every 6 months over the course of 2–5 years. Assessments included ambulatory function and steroid use. The annualized change in 6MWD (Δ6MWD) was studied between all pairs of visits separated by 8–16 months. Prediction models were developed using multivariable regression for repeated measures, and evaluated using cross-validation. Results Among n = 191 follow-up intervals (n = 39 boys), mean starting age was 9.4 years, mean starting 6MWD was 351.8 meters, and 75% had received steroids for at least one year. Over the subsequent 8–16 months, mean Δ6MWD was -37.0 meters with a standard deviation (SD) of 93.7 meters. Predictions based on a composite of age, baseline 6MWD, and steroid use explained 28% of variation in Δ6MWD (R2 = 0.28, residual SD = 79.4 meters). A broadened prognostic model, adding timed 10-meter walk/run, 4-stair climb, and rise from supine, as well as height and weight, significantly improved prediction, explaining 59% of variation in Δ6MWD after cross-validation (R2 = 0.59, residual SD = 59.7 meters). Conclusions A prognostic model incorporating timed function tests significantly improved prediction of 1-year changes in 6MWD. Explained variation was more than doubled compared to predictions based only on age, baseline 6MWD, and steroid use. There is significant potential for composite prognostic models to inform DMD clinical trials and clinical practice.

Daclatasvir + sofosbuvir versus standard of care for hepatitis C genotype 3: a matching-adjusted indirect comparison

AIMS To compare the efficacy and tolerability of daclatasvir and sofosbuvir (DCV + SOF) versus SOF and ribavirin (SOF + R) and versus peginterferon-alfa plus ribavirin (A/R) in patients infected with hepatitis C genotype 3. PATIENTS & METHODS Clinical trials of SOF + R or A/R were identified in systematic literature reviews. The DCV+SOF population was adjusted via propensity score weighting to match average baseline characteristics to those reported for the comparator regimens. RESULTS The SVR12 rate was similar between DCV + SOF and SOF + R, and significantly higher with DCV + SOF than A/R. Rates of discontinuation due to AEs were similar or significantly lower in patients treated with DCV + SOF than SOF + R or A/R. CONCLUSION With its high efficacy and improved tolerability, DCV + SOF is an important treatment for hepatitis C genotype 3.

Patterns of Disease Monitoring and Treatment Among Patients With Tuberous Sclerosis Complex-related Angiomyolipomas

OBJECTIVE To use the tuberous sclerosis complex (TSC) Natural History Database to describe monitoring and treatment patterns among patients with TSC-related angiomyolipomas (AMLs). METHODS This study used the TSC Natural History Database, which contains demographics, affected areas, diagnosis, and treatments for more than 1300 patients with TSC enrolled in 16 participating clinics during 2006-2013. Patient characteristics, AML monitoring tests, and AML treatments were assessed. RESULTS Among the 621 patients with TSC-related AMLs, 54% were female; 77% were Caucasian. Median age at TSC diagnosis was <1 year, whereas median age at AML diagnosis was 9.8 years. Most patients (84%) had at least 1 monitoring test following AML diagnosis. The most commonly used tests were magnetic resonance imaging (MRI; 65% of patients), ultrasound (62%), and computed tomography (41%). Between 2000 and 2012, MRI made up an increasingly large proportion of the total number of monitoring tests. Once diagnosed, 155 (25%) of patients received treatment for AML. The median time from diagnosis to first treatment was 3.8 years. The most common treatments were embolization (10%), everolimus (9%), sirolimus (6%), and nephrectomy (6%). The rate of nephrectomies declined over time, with none conducted during 2011 and 2012. No subsequent surgeries were reported among the 71 patients who received mTOR inhibitor as first-line therapy. CONCLUSION The use of MRIs increased between 2000 and 2012 among patients with TSC-AML. The majority of these patients did not receive treatment for AML. Use of nephrectomy decreased over the study period and was particularly rare in patients who received an mTOR inhibitor.

Epilepsy treatment patterns among patients with tuberous sclerosis complex

INTRODUCTION Tuberous sclerosis complex (TSC) is a rare congenital disorder often associated with epilepsy. However, real-world treatment patterns for epilepsy in patients with TSC are not yet well categorized. METHODS This study included patients with TSC and epilepsy from fifteen clinics in the United States and one in Belgium who were enrolled in the TSC Natural History Database (2006-2014). Patient demographics and epilepsy treatment patterns, including the use of anti-epileptic drugs (AEDs), epilepsy surgeries, and dietary therapies were assessed. RESULTS Of the 1328 patients with TSC in the database, 1110 (83.6%) were diagnosed with epilepsy. The median age of epilepsy diagnosis was 0.7 years. Of those who received treatment for epilepsy (92.3%), 99.5% were prescribed AEDs, 25.3% underwent surgery, 7.9% were prescribed special diets, and 1% were prescribed mammalian target of rapamycin (mTOR) inhibitors. Of the patients receiving AEDs, over half (64.5%) used ≥3 different AEDs, and 22.5% underwent surgical treatment following AED initiation. Of the patients who underwent surgery, 35.1% had subsequent surgery. CONCLUSION The use of multiple AEDs and surgical interventions may indicate a need for new therapies to reduce the treatment burden among patients with TSC and epilepsy.

Corrigendum to “Categorizing natural history trajectories of ambulatory function measured by the 6-minute walk distance in patients with Duchenne muscular dystrophy” [Neuromuscular Disorders 26/9 (2016) 576–583]

Corrigendum to “Categorizing natural history trajectories of ambulatory function measured by the 6-minute walk distance in patients with Duchenne muscular dystrophy” [Neuromuscular Disorders 26/9 (2016) 576–583] Eugenio Mercuri*, James Edward Signorovitch, Elyse Swallow, Jinlin Song, Susan J. Ward for the DMD Italian Groupcollaborative Trajectory Analysis Project (cTAP) Paediatric Neurology Unit, Catholic University, Rome, Italy Analysis Group, Inc., 111 Huntington Ave, 10th Floor, Boston, MA, USA The TAP Collaboration, One Broadway, 14th Floor, Cambridge, MA, USA

Outcomes of second targeted therapy in metastatic renal carcinoma: A retrospective chart review in the EU.

558 Background: This study describes the real-world outcomes of metastatic renal cell carcinoma (mRCC) patients treated with everolimus (EVE), sorafenib (SOR), and axitinib (AXI) as 2nd targeted therapy in the UK, Germany, and France. Methods: A retrospective chart review was conducted among oncologists and urologists in the UK, Germany and France. Charts were reviewed for adult mRCC patients satisfying the following eligibility criteria: 1) experienced disease progression on 1st targeted therapy with sunitinib or pazopanib; 2) initiated 2nd targeted therapy with EVE, AXI, or SOR between 10/2012 and 6/2013. Kaplan-Meier analysis was used to estimate overall survival (OS) after initiation of 2nd targeted therapy among all patients and stratified by type of 2nd targeted therapy. Results: A total of 281 charts were reviewed, with 99, 91, and 91 mRCC patients receiving EVE, AXI, and SOR as 2nd targeted therapy, respectively. Mean age was 60.6 years old at initial mRCC diagnosis and 65.5% were male. The majori...