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/

Treatment outcomes in HIV-infected adolescents attending a community-based antiretroviral therapy clinic in South Africa

<p>Abstract</p> <p>Background</p> <p>Very few data are available on treatment outcomes of adolescents living with HIV infection (whether perinatally acquired or sexually acquired) in sub-Saharan Africa. The present study therefore compared the treatment outcomes in adolescents with those of young adults at a public sector community-based ART programme in Cape Town, South Africa.</p> <p>Methods</p> <p>Treatment outcomes of adolescents (9-19 years) were compared with those of young adults (20-28 years), enrolled in a prospective cohort between September 2002 and June 2009. Kaplan-Meier estimates and Cox proportional hazard models were used to assess outcomes and determine associations with age, while adjusting for potential confounders. The treatment outcomes were mortality, loss to follow-up (LTFU), immunological response, virological suppression and virological failure.</p> <p>Results</p> <p>883 patients, including 65 adolescents (47 perinatally infected and 17 sexually infected) and 818 young adults, received ART. There was no difference in median baseline CD4 cell count between adolescents and young adults (133.5 vs 116 cells/μL; <it>p </it>= 0.31). Overall mortality rates in adolescents and young adults were 1.2 (0.3-4.8) and 3.1 (2.4-3.9) deaths per 100 person-years, respectively. Adolescents had lower rates of virological suppression (< 400 copies/mL) at 48 weeks (27.3% vs 63.1%; <it>p </it>< 0.001). Despite this, however, the median change in CD4 count from baseline at 48 weeks of ART was significantly greater for adolescents than young adults (373 vs 187 cells/μL; <it>p </it>= 0.0001). Treatment failure rates were 8.2 (4.6-14.4) and 5.0 (4.1-6.1) per 100 person-years in the two groups. In multivariate analyses, there was no significant difference in LTFU and mortality between age groups but increased risk in virological failure [AHR 2.06 (95% CI 1.11-3.81; <it>p </it>= 0.002)] in adolescents.</p> <p>Conclusions</p> <p>Despite lower virological suppression rates and higher rates of virological failure, immunological responses were nevertheless greater in adolescents than young adults whereas rates of mortality and LTFU were similar. Further studies to determine the reasons for poorer virological outcomes are needed.</p

Health Care for Youth Involved with the Correctional System

Adolescents with involvement in the correctional system have significant health risks and needs. Professional guidelines and policies related to health services in correctional settings can help health care providers who work in youth detention facilities and those who see youth for follow-up care after incarceration. Several challenges exist to providing care in detention facilities, but overcoming these barriers to optimally serve youth is critical. When youth are released to their homes, community providers must understand the extent of care offered in detention facilities, the unique considerations for youth on probation, and the aspects of follow-up care that should be addressed

Refeeding Hypophosphatemia in Hospitalized Adolescents With Anorexia Nervosa: A Position Statement of the Society for Adolescent Health and Medicine

Refeeding hypophosphatemia in hospitalized adolescents with anorexia nervosa is correlated with degree of malnutrition. Therefore, when initiating nutritional rehabilitation, clinicians should have a heightened awareness of the possibility of refeeding hypophosphatemia in severely malnourished patients (&lt;70% median body mass index)

Condom Availability in Schools: A Practical Approach to the Prevention of Sexually Transmitted Infection/HIV and Unintended Pregnancy.

Adolescents and young adults are highly impacted by sexually transmitted infections (STIs) and unplanned pregnancy in the United States and globally. Consistent and correct use of male latex condoms is associated with protection against both STIs and pregnancy. Providing adolescents and young adults with access to free condoms in schools may increase the use of condoms by improving condom availability, eliminating cost, and decreasing embarrassment associated with purchasing condoms. Studies demonstrate that condom availability in schools is associated with the increased use of condoms and improved overall sexual health. The Society for Adolescent Health and Medicine encourages schools to make condoms available to students as part of efforts to decrease rates of STIs and unplanned pregnancy in adolescents and young adults. The Society for Adolescent Health and Medicine also encourages health care providers to advocate for and support the availability of condoms in local schools