Dalbavancin in Real Life: Economic Impact of Prescription Timing in French Hospitals

Dalbavancin use was almost always associated with a sizable reduction in the LoS. Consequently, the resulting budget impact produced savings or extra costs depending on the chosen scenario. To our knowledge, this is the largest study assessing the impacts of dalbavancin on LoS and budgets for multiple indications in real-life conditions.

Since the demonstration of efficacy on ABSSSIs and excellent tolerance with 1000 mg and 500 mg administered a week apart [7], a recent study confirmed comparable efficacy and increased patient satisfaction with 1500 mg given once [21]. ABSSSIs concern a significant proportion of patients, and the prolonged half-life of dalbavancin makes early discharge of the patients possible. In fact, the economic burden of ABSSSIs and the benefit of early discharge in this context have been largely confirmed [22]. Consequently, two modelling studies showed the benefit of dalbavancin on the LoS [12, 23] and the economic impact [12] in a European context. In accordance with our results, dalbavancin use was not associated with any additional cost, as the incremental cost of dalbavancin was offset by the decrease in requested resources for its use [12]. Additionally, in accordance with the economic model developed for Germany, dalbavancin has the potential to create an average savings of 2964.0 € for MRSA ABSSSIs and BJIs [14]. Similarly, a meta-analysis showed that dalbavancin could save third-party payers $1442.0 to $4803.0 per complicated skin and soft-tissue infection (cSSTI) [24]. Moreover, potential health risks associated with prolonged hospitalization should be taken into account, as well as the improvement in the quality of life related to early discharge. Beyond the hospital perspective, a small study also suggested decreased direct and indirect costs for self-pay (i.e. uninsured, usually with a low income) patients with ABSSSIs who were switched to dalbavancin after discharge [18].

Although dalbavancin use is supposed to be dedicated to ABSSSIs, it is widely used off-label [25] as a preferred antibiotic owing to its efficacy, good tissue penetration and excellent activity against streptococci and staphylococci as well as its long half-life. Our results are also in accordance with an RCT showing a significant and considerable reduction of more than 2 weeks in the LoS for patients treated with dalbavancin for BJIs [15.8 days in the dalbavancin group vs. 33.3 days in the standard of care group (P < 0.001)] [6]. Unsurprisingly, more than half of the patients from our cohort were indeed treated for BJI. This is similar to the study by Bouza et al. [16], where dalbavancin was the third antibiotic used, except for two patients for whom it was a second-line treatment and where the standard of care was daptomycin. It should be noted that no patient treated with dalbavancin under compassionate use was included in this study, which has been the preferred use of dalbavancin for a long time. Consequently, and similar to our study, dalbavancin provided an overall cost reduction of 3064.0 € when used as a second- or third-line treatment. However, the estimation for cost reduction was done by comparison to the theoretical cost of daptomycin treatment for an inpatient on the basis of expert opinion, without comparison to real patients. Another real-life study of dalbavancin use in a US context suggested a mean cost savings of US $40,414 per patient [17]. Again, it was compared to a theoretically expected LoS for standard of care. A common reason for choosing dalbavancin was concerns for the PICC line, whether because of drug addiction or another relative contraindication to the PICC line. Nair et al. [26] also reported that the cost of the drug was often offset by an earlier discharge made possible by dalbavancin. Finally, a multicentre retrospective study from the USA also showed a reduction in the LoS compared to the usual duration and suggested potential savings but without formal cost analysis [27]. Dalbavancin was then used as a bridge with its usual comparator after a median duration of 13.5 days. In addition to the reduction in LoS, Marcellusi et al. also highlighted the reduction in PICC-related adverse events, as PICCs are not necessary for dalbavancin administration, and drug adverse events compared to vancomycin. These results are important from a healthcare insurance perspective due to the economic impact. However, many studies also highlighted the benefit of dalbavancin use in patient quality of life and time savings for healthcare providers, although not formally assessed yet [16, 21, 28].

By making an earlier discharge possible, the maximum benefit of dalbavancin is obtained with early use (first- or second-line treatment, within less than 7 to 11 days after hospitalization). Implementing dalbavancin in short delays advocates for documented use. Therefore, we suggest that dalbavancin should be recommended as an early documented treatment rather than for compassionate use after failures of other treatments, as many “new” antibiotics are often used.

Another noticeable result is the greatest benefit of dalbavancin use among patients who should have requested a deep venous catheter. Indeed, dalbavancin makes the discharge of patients possible without waiting for the placement of a catheter, which is often the reason for a late discharge of patients. Transcutaneous catheters are easier (and faster) to obtain than deep venous catheters, and dalbavancin provides a more modest benefit. We also assessed the impact of dalbavancin use on moderate and severe patient severity, as the use of a costly antimicrobial could add to the already costly stay of the most severe patients. However, we showed that this was not necessarily the case under the condition of an early switch. The greater benefit of using dalbavancin among patients with the most severe disease could be related to a better tolerance or efficacy when compared to vancomycin or daptomycin, but we cannot exclude a recruitment bias wherein patients would have been slightly less severe when receiving dalbavancin instead of vancomycin or daptomycin.

Our results also highlight the evolution in dalbavancin use. Bouza illustrated predominantly off-label use in 2016–2017, with only 21.7% of 69 patients treated for ABSSSIs, and dalbavancin was initiated after a median (IQR) of 2 (1–3) antibiotics and 18.0 (9.8–50.5) days [16]. Dinh et al. reported dalbavancin use in 17.3% of patients with ABSSSIs in 2017–2018 in France with a mean (SD) of 2.3 (1.2) prior antibiotics for a median (min–max) of 22.5 (14.3–39.8) days before dalbavancin [25]. Our cohort, gathered in 2019, was very similar to that of Dinh et al. except for a lower number of prior antibiotic treatments, with a mean (SD) of 1.6 (1.3) (p < 0.001) and a shorter delay of 11.0 (4.0–24.0) days (p < 0.001) (Supplementary Table 3). This illustrates the shift towards a more precocious use of dalbavancin.

In the framework of a microcosting approach, similar efficacy between dalbavancin and its relevant comparators, vancomycin and daptomycin, is assumed, and the focus is on the economic impact. Noninferior efficacy has been shown whether as a first-line treatment or as “bridge use”, which could be an early switch or a late switch from various treatments. This could be regarded as a limitation, but the aim of this study was to perform a budget impact analysis based on real-life patients with a microcosting approach, hence the assumption of similar efficacy. Moreover, there are currently not enough data available to stratify precisely according to infection sites and types and pathogens. Finally, there is nonetheless a sizable amount of available scientific literature indicating that dalbavancin is at least noninferior to vancomycin and daptomycin. However, further studies are necessary to identify optimal situations for dalbavancin use and, more importantly, suboptimal situations if any.

We chose to be conservative in our choices to avoid favouring dalbavancin. Consequently, we excluded outpatients, although a significant number of patients were exclusively managed as outpatients, highlighting the benefit of dalbavancin in limiting unnecessary hospitalization days. Specific costs associated with vancomycin, voluntarily excluded as they may vary, would nonetheless decrease the potential extra cost related to dalbavancin use. Similarly, daptomycin costs were calculated for a low dosage of 8 mg/kg/day, while the current trend is to use 10 mg/kg/day. Therefore, we are confident that we did not overestimate the benefit of using dalbavancin but rather provided a minimal expected estimate. Our results also reflect the current mode of financing dalbavancin because of a hospital perspective and an exclusive “intra-DRG” dalbavancin financial model. A probable evolution of financing dalbavancin in its outpatient parenteral antibiotic therapy (OPAT) use (2nd infusion or more) may increase its cost-effectiveness for hospitals. Therefore, a French national payer perspective is needed.

Antimicrobial stewardship has aimed to reduce antibiotic selection pressure by shortening hospital stay to limit nosocomial infections. Therefore, dalbavancin, whether as a first-line treatment or as a “bridge therapy” after vancomycin or daptomycin, should now be regarded as a relevant option for antimicrobial stewardship. This raises the necessity to identify patients for whom dalbavancin use should be anticipated in advance. It could be dedicated to patients for whom long parenteral antibiotic therapy is indicated, such as for those with orthopaedic prosthesis infections or with IE when there is documented microbiological evidence. However, within a more conceptual framework, predictors for the need for a long half-life treatment should be sought, as already published for ABSSSIs [29]. Unsurprisingly, such predictors are in accordance with the literature (IV drug abuse) and our results (high number of comorbidities, severe patients, etc.). We revised the decision tree proposed for ABSSSIs [29] on the basis of these predictors to adapt to the current trends in dalbavancin use and suggested a strategy to help clinicians identify situations where dalbavancin would be useful and potentially cost-effective (Fig. 4).

We observed important heterogeneity in dosing (Table 1). Indeed, the optimal dosing strategy has yet to be defined. A recent systematic review supports either an initial load of 1000 mg followed by a weekly dose of 500 mg or two 1500 mg doses administered a week apart, both being validated by pharmacokinetics/pharmacodynamics studies [11], while 1500 mg once for ABSSSI is also validated [30, 31]. Regarding previously assessed and published strategies, as well as our results on budget impact, we wish to propose some dosing strategies. A first regimen of 1000 mg + 500 mg a week later (or 1500 mg once) could be appropriate for infections usually requiring a treatment duration of less than 2–3 weeks and a second regimen of 1500 mg + 1500 mg 2 weeks later when a treatment of 4–6 weeks is required. More studies are necessary to validate this proposal, but Austrian expert-based OPAT guidelines propose a single shot of 1500 mg of dalbavancin at days 1 and 8 for osteomyelitis and prosthetic infections, regarded as sufficient for an 8-week therapy. For IE, they also recommend 1500 mg at day 1, followed by 1000 mg at day 15, possibly repeated every 15th day.