Real-world study of direct medical and indirect costs and time spent in healthcare in patients with chronic graft versus host disease.

Chronic graft versus host disease (cGVHD) is a debilitating and costly complication following haemopoietic stem cell transplantation (HSCT). This study describes the economic burden associated with cGVHD. Direct costs associated with specialised healthcare utilisation (inpatient admissions and outpatient visits), as well as indirect costs associated with sickness absence-associated productivity loss were estimated in patients who underwent allogeneic HSCT in Sweden between 2006 and 2015, linking population-based health and economic registers. To capture the period of chronic GVHD, patients were included who survived > 182 days post-HSCT (start of follow-up), and cGVHD was classified based on patient treatment records to correct for any diagnosis underreporting. Patients were classified as 'non-cGVHD' if they received no immunosuppressive treatment, 'mild cGVHD' if they received only systemic corticosteroid treatment or immunosuppressive treatment, or 'moderate-severe cGVHD' if they received extracorporeal photopheresis (ECP) only, corticosteroid treatment and immunosuppressive treatment, or systemic corticosteroid treatment and ECP treatments. Patients with moderate-severe cGVHD spent more time in healthcare, had higher healthcare resource costs and higher sickness absence-related productivity loss compared to patients with non- or mild cGVHD. The cumulative total costs during the first 3 years of follow-up were EUR 14,887,599, EUR 20,544,056, and EUR 47,811,835 for non-, mild, and moderate-severe groups, respectively. The long-term costs incurred with cGVHD following HSCT continue to be very high and significantly impacted by cGVHD severity. This study adds real-world health resource and economic insight relevant for policy-makers and healthcare providers when considering the clinical challenge of balancing immunosuppression to reduce cGVHD.

Front-line treatment of patients with chronic lymphocytic leukemia: a systematic review and network meta-analysis.

AIM: A systematic literature review and network meta-analysis were conducted to determine the relative efficacy and safety of interventions for treatment-naive chronic lymphocytic leukemia patients, as comparative evidence is scarce. MATERIALS & METHODS: Relative treatment effects of progression-free survival, overall survival and safety outcomes were estimated via network meta-analysis based on data identified via systematic literature review. RESULTS: Ibrutinib was superior in all pairwise comparisons for progression-free survival (probability to be better [P] range: overall population: 69-100%; fludarabine-ineligible population: 69-100%) and overall survival (P range: overall: 89-100%; fludarabine-ineligible: 91-100%) and had the highest probability of being best for all outcomes. CONCLUSION: Ibrutinib provides superior benefit in survival and safety compared with other front-line treatments of chronic lymphocytic leukemia.

Impact of novel agents on patient-relevant outcomes in patients with previously untreated chronic lymphocytic leukemia who are not eligible for fludarabine-based therapy.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is an orphan disease that primarily affects the elderly. The majority of symptomatic patients eligible for frontline treatment are unfit for fludarabine based chemoimmunotherapy. Historical treatment includes chlorambucil (Chl), bendamustine/rituximab (BR), and chlorambucil/rituximab/ChlR combination. Clinical guidelines now recommend the use of novel agents, such as ibrutinib (Ibr), in both frontline and relapse settings and other novel agents, such as idelalisib (with rituximab), in relapse settings. Despite compelling clinical results for novel agents, follow-up in clinical trials is relatively short and, thus, the comparative long-term benefits are still unknown. MATERIALS AND METHODS: The authors developed a simulation model to generate treatment specific lifetime estimates of Overall Survival (OS) and Quality Adjusted Life Years (QALYs) for treatment with BR, Chl, ChlR, and Ibr. Two potential clinical scenarios were modelled: with and without novel agents for treating CLL. The model was based on health states relating to first- and second-line progression-free survival (PFS), post-progression survival, and death. RESULTS: Where novel agents were assumed unavailable, mean OS ranged from 5.4-8.5 years and QALYs from 3.5-6.1. Where novel agents were available, the mean OS increased to 10.0 years, with a corresponding increase in QALYs to 7.6. Frontline Ibr use followed by Physician's Choice, including novel agents at relapse, resulted in projected increase in OS of between 18% (1.5 years) and 85% (4.6 years), corresponding to a 25-117% increase in QALYs, compared with currently available traditional therapies. LIMITATIONS: The limitations of this analysis include immature OS data and the assumption of equivalent efficacy across all novel agents in terms of their impact on PFS and OS. CONCLUSIONS: The use of novel agents is predicted to yield substantive gains in predicted lifetime OS and QALY improvements compared to traditional therapies in CLL patients who are ineligible for fludarabine-based chemoimmunotherapy.

Comparative Efficacy of Ibrutinib Versus Obinutuzumab + Chlorambucil in First-Line Treatment of Chronic Lymphocytic Leukemia: A Matching-Adjusted Indirect Comparison.

INTRODUCTION: Ibrutinib (ibr) monotherapy and the combination of obinutuzumab plus chlorambucil (obi) are approved for previously untreated chronic lymphocytic leukemia (CLL). No trials directly comparing their efficacy are available. Therefore a matching-adjusted indirect comparison (MAIC) was performed to provide insight into their relative efficacy in terms of progression-free survival (PFS) and overall survival (OS). MAIC attempts to adjust for between-trial differences in factors known or suspected to influence treatment effects, to minimize bias. METHODS: A MAIC within a Bayesian framework was conducted using individual patient data from the RESONATE-2 study of ibr versus chlorambucil and published data from the CLL11 study of obi versus chlorambucil. Both studies were conducted in patients ineligible for full-dose fludarabine-based therapy. After matching, the reweighted adjusted relative efficacy measure of ibr versus chlorambucil from RESONATE-2 [hazard ratio (HR), 95% credible interval (CrI)] was compared with that of obi versus chlorambucil from CLL11 for each endpoint, using a Bayesian indirect comparison. RESULTS: Our results suggest that in a population with similar average baseline characteristics to CLL11, ibr would improve PFS and OS outcomes compared to obi. Before matching, the HRs for ibr versus obi were 0.48 [CrI = 0.22-1.02, p(HR <1) = 97%], 0.85 [CrI = 0.44-1.63, p(HR <1) = 69%], and 0.40 [CrI = 0.10-1.54, p(HR <1) = 91%] for PFS by investigator assessment, PFS by independent review committee, and OS, respectively. After matching on all available characteristics the HRs decreased to 0.12 [CrI = 0.02-0.97, p(HR <1) = 98%], 0.24 [CrI = 0.04-1.35, p(HR <1) = 95%], and 0.21 [CrI = <0.01-8.89, p(HR <1) = 79%], respectively. There was a large variance around the treatment effect for OS due to the low number of deaths. CONCLUSION: Our analysis suggests that ibrutinib is highly likely to provide greater PFS benefit than obinutuzumab plus chlorambucil in older or less fit patients with previously untreated CLL. There is also an indication of improvement in OS, albeit with a higher uncertainty due to the low number of events. FUNDING: Janssen-Cilag Ltd.

Cost-effectiveness of peginterferon alpha-2a and peginterferon alpha-2b combination regimens in genotype-1 naive patients with chronic hepatitis C.

BACKGROUND/AIMS: Pegylated interferons (Peg-IFNs) with ribavirin represent the standard treatment in chronic C viral hepatitis in Romania. Primary aim was to evaluate the cost-effectiveness of Peg-IFN alpha-2a plus ribavirin versus IFN alpha-2b plus ribavirin in genotype-1 patients in Romanian setting. The second end point was to make an indirect comparison of the cost-effectiveness of combination therapy of the two Peg-IFNs. METHODOLOGY: Published clinical data on sustained virological response rates (SVR) and early virological response rates (EVR) from more recent published studies were used for both combination therapies. A Markov model with seven health states was built. The reference patient was a 45-year-old male with chronic non-cirrhotic liver disease due to chronic HCV infection. Time horizon is patient lifetime. Published data on the natural history of hepatitis C, local mortality data, published utilities and local expertise were used for assessment of local procedures, resources used and costs. The perspective is that of the National Health Insurance Agency (NHIA). RESULTS: The incremental cost of treatment with Peg-IFN alpha-2a plus ribavirin is 19,056 Rol per LY gained and 27,175 Rol per QALY gained. A one-way sensitivity analysis showed that results are sensitive to the discount rate used, but they still are highly cost-effective. The indirect comparison of cost-effectiveness of Peg-IFNs combination therapies over IFN alpha-2b showed superiority of Peg-IFN alpha-2a and ribavirin therapy. CONCLUSION: This study demonstrates a higher cost-effectiveness of the current state-of-the art treatment with Peg-IFN alpha-2a with ribavirin over the standard IFN and ribavirin combination. Although a slight superiority of Peg-IFN alpha-2a over Peg-IFN alpha-2b combined regimen was shown in Romanian setting in terms of LYs and QALYs gained, there are no significant differences in cost-effectiveness of the two therapies.