Gisela Hostenkamp

Direct comparison of treatment responses, remission rates, and drug adherence in patients with rheumatoid arthritis treated with adalimumab, etanercept, or infliximab: Results from eight years of surveillance of clinical practice in the nationwide Danish DANBIO registry

OBJECTIVE To compare tumor necrosis factor alpha inhibitors directly regarding the rates of treatment response, remission, and the drug survival rate in patients with rheumatoid arthritis (RA), and to identify clinical prognostic factors for response. METHODS The nationwide DANBIO registry collects data on rheumatology patients receiving routine care. For the present study, we included patients from DANBIO who had RA (n = 2,326) in whom the first biologic treatment was initiated (29% received adalimumab, 22% received etanercept, and 49% received infliximab). Baseline predictors of treatment response were identified. The odds ratios (ORs) for clinical responses and remission and hazard ratios (HRs) for drug withdrawal were calculated, corrected for age, disease duration, the Disease Activity Score in 28 joints (DAS28), seropositivity, concomitant methotrexate and prednisolone, number of previous disease-modifying drugs, center, and functional status (Health Assessment Questionnaire score). RESULTS Seventy percent improvement according to the American College of Rheumatology criteria (an ACR70 response) was achieved in 19% of patients after 6 months. Older age, concomitant prednisolone treatment, and low functional status at baseline were negative predictors. The ORs (95% confidence intervals [95% CIs]) for an ACR70 response were 2.05 (95% CI 1.52-2.76) for adalimumab versus infliximab, 1.78 (95% CI 1.28-2.50) for etanercept versus infliximab, and 1.15 (95% CI 0.82-1.60) for adalimumab versus etanercept. Similar predictors and ORs were observed for a good response according to the European League Against Rheumatism criteria, DAS28 remission, and Clinical Disease Activity Index remission. At 48 months, the HRs for drug withdrawal were 1.98 for infliximab versus etanercept (95% 1.63-2.40), 1.35 for infliximab versus adalimumab (95% CI 1.15-1.58), and 1.47 for adalimumab versus etanercept (95% CI 1.20-1.80). CONCLUSION Older age, low functional status, and concomitant prednisolone treatment were negative predictors of a clinical response and remission. Infliximab had the lowest rates of treatment response, disease remission, and drug adherence, adalimumab had the highest rates of treatment response and disease remission, and etanercept had the longest drug survival rates. These findings were consistent after correction for confounders and sensitivity analyses and across outcome measures and followup times.

The impact of recent chemotherapy innovation on the longevity of myeloma patients: US and international evidence

The longevity of multiple myeloma patients increased sharply since the late 1990s. This increase coincided with the introduction of several important innovations in chemotherapy for myeloma. In this study, we aim to quantify the impact of recent chemotherapy innovation on the longevity of myeloma patients using both time-series US data and longitudinal data on 38 countries. We estimate that almost two-thirds (0.99 years) of the 1997-2005 increase in the life expectancy of American myeloma patients was due to an increase in the number of chemotherapy regimens now preferred by specialists. Based on a back-of-the-envelope calculation, this means that the cost per US life-year gained from post-1997 chemotherapy innovation is unlikely to have exceeded

Are fish eaters healthier and do they consume less health-care resources?

46,000. We also investigate the impact of chemotherapy innovation on the myeloma mortality rate using longitudinal country-level data on 38 countries during the period 2002-2012. Countries that had larger increases in the number of chemotherapy regimens now preferred by specialists had larger subsequent declines in myeloma mortality rates, controlling for myeloma incidence. The (marginal) effect on the mortality rate of one additional preferred chemotherapy regimen is similar in other countries to its effect in the US. Non-US prices of two of the three new drugs were lower than US prices, so recent myeloma chemotherapy innovation may have been more cost-effective in other countries than it was in the US. Recent chemotherapy innovation has had a significant positive impact on the longevity of myeloma patients in the countries in which the drugs have been available.

Drug safety and the impact of drug warnings: An interrupted time series analysis of diabetes drug prescriptions in Germany and Denmark

OBJECTIVE Regular dietary intake of fish is associated with reduced risk of developing cardiovascular and other chronic diseases, and may improve general well-being. If fish eaters are healthier, they may use fewer health-care resources. The present study aimed to describe the reported intake of fish and fish products in a Danish general population, and to investigate whether fish consumption is associated with generic measures of self-reported health and consumption of health-care resources. DESIGN Data on eating patterns and health status for 3422 Danish adults were obtained by telephone interview in the Funen County Health Survey. These data were merged with individual-level register data on health-care utilisation. Survey respondents were categorised into those consuming fish at least once weekly (fish eaters) and those consuming fish less frequently (non-fish eaters). RESULTS People who reported eating fish twice monthly or once weekly had significantly better overall self-reported health than those who rarely eat fish, even after adjustment for age, gender, social characteristics and lifestyle factors. Fish eaters did not have significantly lower aggregated health-care costs, although their hospital utilisation was significantly lower than that for non-fish eaters. CONCLUSIONS Moderate fish consumption was associated with better self-reported general health even after controlling for possible confounding variables. Overall, fish eaters appeared to use the same amount of health-care resources as non-eaters, although fish eaters used more medicine but were less likely to be admitted to a hospital.

The Health Gradient and Early Retirement: Evidence from the German Socio-economic Panel

OBJECTIVE To analyse the impact of drug safety warnings from the European Medicines Agency (EMA) on drug utilisation and their interaction with information released through national reimbursement bodies. METHODS Insurance claims data on anti-diabetic drug prescriptions in primary care in Germany and Denmark were analysed using interrupted time series analysis, with EMA drug warnings for thiazolidinediones (TZDs) in 2007 and 2011 as the intervention. Monthly drug utilisation data per substance in defined daily dosages (DDD) consumed per 1000 insurees were retrieved from the Danish national drug prescriptions register and one large statutory sickness fund in Germany. RESULTS TZDs were generally reimbursed in Germany but restricted to individual reimbursement in Denmark. Consequently, utilisation of TZDs was much higher in Germany in 2007 compared with Denmark. For rosiglitazone, the drug warning had a significant impact on utilisation, reducing the number of DDD per 1000 insurees per day by -0.0105 in Denmark and -0.0312 in Germany (p-values<0.05). For pioglitazone, neither of the drug warnings had a significant effect on utilisation. CONCLUSION The impact of EMA drug warnings differed across countries and might be mediated by information released through national reimbursement bodies and physician associations. Increasing complexity of new drugs and modified approval procedures require a strengthening of information exchange between drug regulation bodies and physicians to ensure patient safety.