Katarina Steen Carlsson

Intermediate-dose versus high-dose prophylaxis for severe hemophilia: comparing outcome and costs since the 1970s

Prophylactic treatment in severe hemophilia is very effective but is limited by cost issues. The implementation of 2 different prophylactic regimens in The Netherlands and Sweden since the 1970s may be considered a natural experiment. We compared the costs and outcomes of Dutch intermediate- and Swedish high-dose prophylactic regimens for patients with severe hemophilia (factor VIII/IX < 1 IU/dL) born between 1970 and 1994, using prospective standardized outcome assessment and retrospective collection of cost data. Seventy-eight Dutch and 50 Swedish patients, median age 24 years (range, 14-37 years), were included. Intermediate-dose prophylaxis used less factor concentrate (median: Netherlands, 2100 IU/kg per year [interquartile range (IQR), 1400-2900 IU/kg per year] vs Sweden, 4000 IU/kg per year [IQR, 3000-4900 IU/kg per year]); (P < .01). Clinical outcome was slightly inferior for the intermediate-dose regimen (P < .01) for 5-year bleeding (median, 1.3 [IQR, 0.8-2.7] vs 0 [IQR, 0.0-2.0] joint bleeds/y) and joint health (Haemophilia Joint Health Score >10 of 144 points in 46% vs 11% of participants), although social participation and quality of life were similar. Annual total costs were 66% higher for high-dose prophylaxis (mean, 180 [95% confidence interval, 163 - 196] × US

Prospective study of patients with injuries to the hand and forearm: Costs, function, and general health.

1000 for Dutch vs 298 [95% confidence interval, 271-325]) × US

Daily dosing prophylaxis for haemophilia: a randomized crossover pilot study evaluating feasibility and efficacy

1000 for Swedish patients; (P < .01). At group level, the incremental benefits of high-dose prophylaxis appear limited. At the patient level, prophylaxis should be tailored individually, and many patients may do well receiving lower doses of concentrate without compromising safety.

Validity of diagnostic codes and prevalence of physician-diagnosed psoriasis and psoriatic arthritis in southern sweden - a population-based register study.

Patients with injured hands and forearms of varying severity [Hand Injury Severity Score (HISS)] were studied prospectively, including analysis of costs, hand/arm function (DASH), and health status (SF-36). Costs, duration of sick-leave, DASH-score (high score; impaired function) increased by severity of injury (higher HISS) and the greatest proportion of total costs resulted from lost production. Most employed patients returned to work within a year, but even minor injuries were expensive. HISS and costs of care during an emergency were significantly associated with duration of sick-leave, although HISS did not fully explain variation in costs and duration of sick-leave. DASH-score at one year was associated with variation in age, HISS, and residual health care costs. Results of DASH and subgroups for physical and bodily pain on SF-36 were consistent. Injuries to hand and forearm may generate high costs for society in terms of health care and long periods of sick-leave (lost production), but even minor injuries should be accounted for.

Costs of on‐demand and prophylactic treatment for severe haemophilia in Norway and Sweden

Regular replacement therapy (prophylaxis) for haemophilia has been shown to prevent development of disabling arthropathy and to provide a better quality of life compared to treatment on demand; however, at a substantially higher cost. Calculations based on pharmacokinetic principles have shown that shortening dose intervals may reduce cost. The aim of this prospective, randomized, crossover pilot study was to address whether daily dosing is feasible, if it reduces concentrate consumption and is as effective in preventing bleeding as the standard prophylactic dosing regimen. In a 12 + 12 month crossover study, 13 patients were randomized to start either their own previously prescribed standard dose, or daily dosing adjusted to maintain at least the same trough levels as obtained with the standard dose. Ten patients completed the study. A 30% reduction in cost of factor concentrates was achieved with daily prophylaxis. However, the number of bleeding events increased in some patients in the daily dosing arm and patients reported decreased quality of life during daily prophylaxis. Daily treatment had a greater impact on daily life, and the patients found it more stressful.Prophylaxis with daily dosing may be feasible and efficacious in some patients. A substantial reduction of factor consumption and costs can be realized, but larger studies are needed before the introduction of daily prophylaxis into clinical routine can be recommended.

Switch to Biological Agent in Psoriasis Significantly Improved Clinical and Patient-Reported Outcomes in Real-World Practice

Objective To validate diagnostic codes for psoriasis and psoriatic arthritis (PsA) and estimate physician-diagnosed prevalence of psoriasis and PsA in the Skåne region, Sweden. Methods In the Skåne Healthcare Register (SHR), all healthcare consultations are continuously collected for all inhabitants in the Skåne region (population 1.2 million). During 2005–2010 we identified individuals with ≥1 physician-consultations consistent with psoriasis (ICD-10). Within this group we also identified those diagnosed with PsA. We performed a validation by reviewing medical records in 100 randomly selected cases for psoriasis and psoriasis with PsA, respectively. Further, we estimated the pre- and post-validation point prevalence by December 31, 2010. Results We identified 16 171 individuals (psoriasis alone: n = 13 185, psoriasis with PsA n = 2 986). The proportion of ICD-10 codes that could be confirmed by review of medical records was 81% for psoriasis and 63% for psoriasis with PsA with highest percentage of confirmed codes for cases diagnosed ≥2 occasions in specialized care. For 19% and 29% of the cases respectively it was not possible to determine diagnosis due to insufficient information. Thus, the positive predicted value (PPV) of one ICD-10 code for psoriasis and psoriasis with PsA ranged between 81–100% and 63–92%, respectively. Assuming the most conservative PPV, the post-validation prevalence was 1.23% (95% CI: 1.21–1.25) for psoriasis (with or without PsA), 1.02% (95% CI: 1.00–1.03) for psoriasis alone and 0.21% (95% CI: 0.20–0.22) for psoriasis with PsA. The post-validation prevalence of PsA in the psoriasis cohort was 17.3% (95% CI: 16.65–17.96). Conclusions The proportion of diagnostic codes in SHR that could be verified varied with frequency of diagnostic codes and level of care highlighting the importance of sensitivity analyses using different case ascertainment criteria. The prevalence of physician-diagnosed psoriasis and PsA confirm other population-based studies, also after adjustment due to misclassification of disease.

Cost and outcome: Comparisons of two alternative bypassing agents for persons with haemophilia A complicated by an inhibitor

Summary.  The expected annual cost (in the year 2000 prices) for a 30‐year‐old patient with average individual and treatment characteristics for on‐demand EUR 51 832 (95% CI: 44 324–59 341) and for prophylaxis EUR 146 118 (95% CI: 129 965–162 271), was obtained from panel‐data analysis of an 11‐year retrospective panel of 156 patients with severe haemophilia in Norway and Sweden. Costs included haemophilia‐related treatment costs within the health‐care sector (factor concentrate, doctors’ visits, diagnostic procedures, hospitalisation, invasive procedures, etc.) and cost for haemophilia‐related resource use in other sectors (lost production, use of special equipment, adaptation of workplace and domicile, etc). Although costs of lost production, reconstructive surgery and hospitalisation were higher for on‐demand, they did not balance out the higher costs of factor‐concentrate consumption in prophylaxis. The cut‐off risk of premature death, where on‐demand and prophylaxis would have been equally costly, was 3.7 percentage units higher for on‐demand than for prophylaxis. Such a great risk difference has not been reported elsewhere to our knowledge. Estimated cost‐elasticities indicated that annual costs of prophylaxis would increase by approximately the same proportion as a potential increase in the price of factor concentrate and decrease less than proportionately with a reduction in prescribed dose kg−1. For on‐demand, the annual costs would increase by approximately the same proportion as an increase in the prescribed dose kg−1.

Costs and outcome for serious hand and arm injuries during the first year after trauma – a prospective study

Background: Although clinical studies have shown efficacy of biological agents in moderate to severe psoriasis, observational studies of real-world effectiveness are rare. Objective: To analyse the psoriasis area and severity index (PASI) and quality of life by the EQ-5D questionnaire and dermatology quality of life index (DLQI) in psoriasis patients who switched from conventional systemic treatment to biological agents in clinical practice. Furthermore, to analyse patient groups with the highest benefit of biological agents. Methods: Longitudinal, observational study based on the Swedish National Registry for Systemic Treatment of Pso-riasis, PsoReg. Outcomes of biological-naïve patients who switched to a biological agent (n = 267) were analysed before switch and at the first follow-up. Results: Patients significantly improved in EQ-5D, DLQI and PASI (p < 0.001). Patients with DLQI ≥10 and/or PASI ≥10 had the greatest benefits from biological agents in terms of EQ-5D. Conclusions: Patients with moderate to severe psoriasis benefit from biological agents in clinical practice; the patients with the highest benefits were those with high pretreatment PASI and DLQI scores.

Digital nerve injuries: Epidemiology, results, costs, and impact on daily life.

The development of inhibitory antibodies to factor VIII is a serious complication of haemophilia. Two haemostatic agents with different bypassing mechanisms have been used in the treatment of patients with inhibitors: activated prothrombin complex concentrate (aPCC) and recombinant factor VIIa (rFVIIa). The objective was to compare cost and outcome of aPCC and rFVIIa in the treatment of joint bleeds. The analyses were based on the FENOC (FEIBA NovoSeven Comparative Study) crossover study where 48 patients used aPCC and rFVIIa to treat two joint bleeds. Incremental cost-effectiveness ratios were calculated for three outcome measures and the variation in cost was analyzed using two alternative regression methods. Results were subjected to sensitivity analyses. Key determinants of cost were prescribed dose, bodyweight and treatment in addition to protocol. The cost of aPCC was on average lower than rFVIIa. At all but one time point, patients rated slightly higher (but not statistically significantly) percentages of treatment efficacy and stopping of the bleed by aPCC. The reported reduction in pain from start of treatment up to 48 hours varied considerably among individuals. The different relative prices in the US, Turkey and Sweden mattered, but did not reverse the main results. In conclusion, the cost per episode was significantly lower for aPCC. The large individual-level variation in reduction of pain supports decisions that consider the individual patients experience and that accept trade-offs between cost and reduction in pain rather than focusing on cost only.

Willingness to pay for on‐demand and prophylactic treatment for severe haemophilia in Sweden

BackgroundTo study costs and outcome for serious hand and arm injuries during the first year after the trauma.MethodsIn patients with a Hand Injury Severity Score (HISS) > 50, DASH and EQ-5D scores as well as factors related to costs within the health care sector, costs due to lost production and total costs were evaluated. Cox-regression analysis stratifying for mechanism of injury was used to analyse return to work.ResultsThe majority of the 45 included patients (median 42 years 16–64) were men with severe (n = 9) or major (n = 36) injuries with different type of injuries (amputations n = 13; complex injuries n = 18; major nerve injuries/full house n = 13; burn injury n = 1). DASH and EQ-5D decreased and increased, respectively, significantly over time during one year. Total costs (+34%) and costs of lost production were highest for persons injured at work. Factors associated with higher health care costs were age >50 years (+52%), injury at work (+40%) and partial labour market activity (+66%). Costs of lost production had a significant role in total costs of injury. Patients with major injuries had longer duration of sick leave. Patients with severe injuries were more likely to return to work [(RR 3.76 (95% CI 1.38-10.22) from Cox regression, controlling for age, gender and presence of nerve injury].ConclusionsDespite the fact that work environments have constantly improved over the last decades, we found that hand injuries at work were most costly both in terms of health care and costs of lost production, although the severity, i.e. HISS, did not differ from injuries occurring at home or during leisure.