The Cost-Effectiveness of Tuberculosis Preventive Therapy for HIV-Infected Individuals in Southern India: A Trial-Based Analysis

Regimens for isoniazid-based preventive therapy (IPT) for tuberculosis (TB) in HIV-infected individuals have not been widely adopted given concerns regarding efficacy, adherence and drug resistance. Further, the cost-effectiveness of IPT has not been studied in India.We used an HIV/TB model to project TB incidence, life expectancy, cost and incremental cost-effectiveness of six months of isoniazid plus ethambutol (6EH), thirty-six months of isoniazid (36H) and no IPT for HIV-infected patients in India. Model input parameters included a median CD4 count of 324 cells/mm(3), and a rate ratio of developing TB of 0.35 for 6EH and 0.22 for 36H at three years as compared to no IPT. Results of 6EH and 36H were also compared to six months of isoniazid (6H), three months of isoniazid plus rifampin (3RH) and three months of isoniazid plus rifapentine (3RPTH).Projected TB incidence decreased in the 6EH and 36H regimens by 51% and 62% respectively at three-year follow-up compared to no IPT. Without IPT, projected life expectancy was 136.1 months at a lifetime per person cost of $5,630. 6EH increased life expectancy by 0.8 months at an additional per person cost of$100 (incremental cost-effectiveness ratio (ICER) of $1,490/year of life saved (YLS)). 36H further increased life expectancy by 0.2 months with an additional per person cost of$55 (ICER of $3,120/YLS). The projected clinical impact of 6EH was comparable to 6H and 3RH; however when compared to these other options, 6EH was no longer cost-effective given the high cost of ethambutol. Results were sensitive to baseline CD4 count and adherence.Three, six and thirty-six-month regimens of isoniazid-based therapy are effective in preventing TB. Three months of isoniazid plus rifampin and six-months of isoniazid are similarly cost-effective in India, and should be considered part of HIV care

The clinical effectiveness and cost-effectiveness of abatacept, adalimumab, etanercept and tocilizumab for treating juvenile idiopathic arthritis: a systematic review and economic evaluation

Background: Juvenile idiopathic arthritis (JIA) is characterised by joint pain, swelling and limitation of movement caused by inflammation. Subsequent joint damage can lead to disability and growth restriction. Treatment commonly includes disease modifying anti-rheumatic drugs (DMARD) such as methotrexate. Clinical practice now favours newer drugs termed biologic DMARDs where indicated.Objective: To assess the clinical and cost-effectiveness of four biologic DMARDs (etanercept, abatacept, adalimumab and tocilizumab - with or without methotrexate where indicated) for the treatment of JIA (systemic or oligoarticular JIA excluded).Data sources: Electronic bibliographic databases including MEDLINE, EMBASE, The Cochrane Library and DARE were searched for published studies from inception to May 2015 for English language articles. Bibliographies of related papers, systematic reviews and company submissions were screened and experts were contacted to identify additional evidence.Review methods: Systematic reviews of clinical-effectiveness, health-related quality of life and cost-effectiveness were undertaken according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. A cost-utility decision analytic model was developed to compare estimated cost-effectiveness of biologic DMARDs versus methotrexate. The base case time horizon was 30 years and the model took a National Health Service (NHS) perspective, with costs and benefits discounted at 3.5%.Results: Four placebo-controlled RCTs met the inclusion criteria for the clinical-effectiveness review (one RCT evaluating each biologic DMARD). Only one RCT included UK participants. Participants had to achieve an American College of Rheumatology Pediatric (ACR Pedi) 30 response to open-label lead-in treatment in order to be randomised. An exploratory adjusted indirect comparison suggests that the four biologic DMARDs are similar with fewer disease flares and greater proportions with ACR Pedi 50 and 70 responses among participants randomised to continued biologic DMARD. However, confidence intervals were wide, the number of trials was low and there was clinical heterogeneity between trials. Open-label extensions of the trials showed that generally ACR responses remained constant or even increased after the double-blind phase. The proportions of adverse events and serious adverse events were generally similar between treatment and placebo groups. Four economic evaluations of biologic DMARDs for patients with JIA were identified but all had limitations. Two quality of life studies were included, one of which informed the cost-utility model. The incremental cost-effectiveness ratio (ICER) for adalimumab, etanercept and tocilizumab versus methotrexate was £38,127, £32,526 and £38,656 per QALY, respectively. The ICER for abatacept versus methotrexate as a second line biologic was £39,536 per QALY.Limitations: The model does not incorporate the natural history of JIA in terms of long-term disease progression, as the current evidence is limited. There are no head-to-head trials of biologic DMARDs and clinical evidence for specific JIA subtypes is limited.Conclusions: Biologic DMARDs are superior to placebo (with methotrexate where permitted) in children with (predominantly) polyarticular course JIA, and an insufficient response to previous treatment. Randomised comparisons of biologic DMARDs with long-term efficacy and safety follow- are needed to establish comparative effectiveness. RCTs for JIA subtypes where evidence is lacking are also required.Funding: The National Institute for Health Research Health Technology Assessment programme. <br/