Inflammatory autoimmune diseases (rheumatoid arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, psoriasis, and psoriatic arthritis) have a considerable impact on patients’ quality of life and healthcare budgets. Biosimilar infliximab (Remsima®) has been authorized by the European Medicines Agency for the management of inflammatory autoimmune diseases based on a data package demonstrating efficacy, safety, and quality comparable to the reference infliximab product (Remicade®). This analysis aims to estimate the 1-year budget impact of the introduction of Remsima in five European countries.
Methods
A budget impact model for the introduction of Remsima in Germany, the UK, Italy, the Netherlands, and Belgium was developed over a 1-year time horizon. Infliximab-naïve and switch patient groups were considered. Only direct drug costs were included. The model used the drug-acquisition cost of Remicade. The list price of Remsima was not known at the time of the analysis, and was assumed to be 10–30% less than that of Remicade. Key variables were tested in the sensitivity analysis.
Results
The annual cost savings resulting from the introduction of Remsima were projected to range from €2.89 million (Belgium, 10% discount) to €33.80 million (Germany, 30% discount). If any such savings made were used to treat additional patients with Remsima, 250 (Belgium, 10% discount) to 2602 (Germany, 30% discount) additional patients could be treated. The cumulative cost savings across the five included countries and the six licensed disease areas were projected to range from €25.79 million (10% discount) to €77.37 million (30% discount). Sensitivity analyses showed the number of patients treated with infliximab to be directly correlated with projected cost savings, with disease prevalence and patient weight having a smaller impact, and incidence the least impact.
Conclusion
The introduction of Remsima could lead to considerable drug cost-related savings across the six licensed disease areas in the five European countries.
The online version of this article (doi:10.1007/s12325-015-0233-1) contains supplementary material, which is available to authorized users.
Introduction
Rheumatoid arthritis (RA), ankylosing spondylitis (AS), Crohn’s disease, ulcerative colitis (UC), psoriasis, and psoriatic arthritis (PsA) are inflammatory autoimmune diseases. These conditions are generally chronic and lifelong, characterized by alternating flare-ups and periods of remission. Given their chronic, and often progressive, nature, they have a considerable impact on patients’ quality of life [1‐5] as well as healthcare budgets [6‐10]. First-line treatments include non-steroidal anti-inflammatory drugs (NSAIDs), conventional disease-modifying anti-rheumatic drugs (cDMARDs; e.g., methotrexate), and topical and/or local corticosteroids; immunosuppressants and systemic corticosteroids are also used [11‐16]. Inhibitors of tumor necrosis factor alpha (TNF-α) have shown good efficacy and an acceptable safety profile in patients after failure of conventional treatments, and in those patients with contraindications to conventional treatments [17‐20]. TNF-α inhibitors are biologics, which are defined as medicines that are produced by cells (ranging from bacterial cells or yeast, to murine or human cell lines), or derived from a biological source.
Infliximab (Remicade®; Janssen Biotech, Inc.) was granted marketing authorization in 1999 [21]. It is a monoclonal antibody and TNF-α inhibitor, indicated in the areas of RA, AS, adult and pediatric Crohn’s disease, adult and pediatric UC, psoriasis, and PsA [21]. The efficacy and safety of infliximab in these disease areas is supported by extensive clinical evidence [16, 22‐26]. Biosimilar infliximab (Remsima®; Celltrion, Inc.) is a biosimilar of Remicade. Biosimilars, in contrast to generics, do not have to be identical to the innovator and/or brand product. The intrinsic complexity of the molecule and their biological derivation means that it is not possible to produce exact copies of the reference product. Biosimilars must demonstrate similarity to the reference product in terms of quality, biological activity, clinical efficacy, and safety [27‐29]. Remsima was authorized in 2013 by the European Medicines Agency (EMA) for the same indications as the reference product Remicade [30]. Remsima was the first biosimilar antibody to meet the stringent EMA criteria for extrapolation of indications [31]. Remsima is supported by two clinical trials in patients with RA (PLANETRA; ClinicalTrials.gov #NCT01217086) [32] and AS (PLANETAS; ClinicalTrials.gov #NCT01220518) [33]. PLANETAS was a Phase I randomized, double-blind, multicenter, multinational, parallel-group study, designed to compare the pharmacokinetics, safety, and efficacy of Remsima and Remicade in 250 patients with AS [33]. PLANETRA was a Phase III, randomized, double-blind, multicenter, multinational, parallel-group study, designed to compare the efficacy and safety of Remsima and Remicade in 605 patients with RA and inadequate response to methotrexate treatment [32]. The pharmacokinetic profiles of Remsima and Remicade were demonstrated to be equivalent [30, 32, 33]. The trials also concluded that Remsima was well tolerated, with an efficacy and safety profile comparable to that of Remicade up to week 30 [30, 32, 33]. These 30-week results have been confirmed by 54-week data and 2-year follow-up extension studies [34‐37].
Anzeige
Biologics, including TNF-α inhibitors, are costly compared with cDMARDs and have led to increased costs to healthcare systems [38]. Remicade has been the subject of several economic analyses (in different disease areas and countries) [39‐44]. The results indicate that Remicade might be cost-effective in some patient groups, but appears unlikely to be cost-effective in others. Furthermore, even in cases where Remicade is cost-effective, any savings made are insufficient to offset the additional drug-acquisition and administration costs [45, 46] (see Appendix A for a nonsystematic literature review on the cost-effectiveness of Remicade).
Remsima is launching in the five European countries (Germany, the UK, Italy, the Netherlands, and Belgium) in 2015. The present budget impact analysis was designed to estimate the budget impact of the introduction of Remsima across the six licensed indications in these five European countries.
Methods
An Excel-based model was developed to estimate the budget impact of the introduction of Remsima for the treatment of RA, AS, Crohn’s disease, UC, psoriasis, or PsA, as per licensed indications in five European countries (Germany, the UK, Italy, the Netherlands, and Belgium).
Population
The population of interest comprised both an infliximab-naïve and a switch (patients currently treated with infliximab) patient population. Patient weight was assumed to be 75 kg [47]. In both populations, a fixed cohort of patients with the disease was analyzed over the 1-year time horizon of the model. The model applied a top-down epidemiological approach (i.e., using the incidence and/or prevalence as basis) to calculate the number of eligible patients who, under current prescribing practice, would be treated with infliximab in each population.
Anzeige
Population estimates for the included countries were obtained from the United Nations [48] (Table 1). Prevalence data applied in the model were sourced via a comprehensive literature search of the PubMed and Embase databases, and supplied by Kantar Health (Epi Database®. Kantar Health. Data on file). Incidence data for the treatment-naïve population were derived from the published literature, and country-specific data were applied if possible (Table 2). In the absence of country-specific incidence data, data were derived from other studies, and assumptions regarding the generalizability and appropriateness of these data were made (Table 2). It was assumed in the model that all patients present at the beginning of the forecast year, with costs reflecting treatment for a year. Selection of incidence and prevalence data was based upon the limited available published evidence. For consistency, where possible, prevalence rates were taken from the same source.
Table 1
Model inputs: population numbers [48] and Remicade vial price (100 mg)
Where a reference source gave a range, a mid-point estimate was used. Values shown have been rounded to the third decimal point
AS ankylosing spondylitis, CD Crohn’s disease, PsA psoriatic arthritis, RA rheumatoid arthritis, UC ulcerative colitis
aEpi Database®. Kantar Health. Data on file
bMusculoskeletal Health in Europe Report v5 [58]. A mean value of the range given (derived from published literature) was used
cTaken from [59], supported by [60]. The consistent data from two such different locations suggest that this incidence rate is likely to be consistent across North America and Europe
dThe incidence for Germany and the UK was assumed to be the same as for The Netherlands
eFor these countries, the incidence was calculated from the UK incidence, weighted based on the prevalence in the respective country
fIncluding one loading dose
gThe SPC indicated that maintenance doses should be administered every 6–8 weeks; therefore, 7 weeks was used for the purpose of this model
hData from The Netherlands were used as proxy
The percentages of patients treated with any medication (i.e., biological [b]DMARDs or cDMARDs) for their condition (termed ‘drug-treated patients’) are presented in Table 3. To these patients, the model applied the proportion of drug-treated patients who receive reference infliximab. The number of drug-treated patients and proportion of patients receiving infliximab (termed ‘patients currently treated with Remicade’) was applied to the cohort of switch and treatment-naïve patients. In the case of treatment-naïve patients, the purpose was to calculate under current prescribing practice the number of patients expected to be treated with infliximab.
Table 3
Model inputs: estimate of percentage of patients treated with medication for their condition (drug-treated patients) and number of patients currently treated with infliximab (Remicade)
%
RA
AS
CD
UC
Psoriasis
PsA
Percentage of drug-treated patientsa
Germany
48.75
48.75b
63.55
81.20
32.89
48.75b
UK
48.75
48.75b
54.70
77.20
63.17
48.75b
Italy
48.75
48.75b
46.44
81.70
44.52
48.75b
The Netherlands
48.75
48.75b
58.94
77.40
44.46
48.75b
Belgium
48.75
48.75b
58.94
77.40
44.46
48.75b
Number of patients currently treated with infliximab (Remicade)c
Germany
1925
1278
11,719
3835
1065
1918
UK
3160
485
6417
988
568
455
Italy
1840
1562
2188
2499
1388
2188
The Netherlands
1070
464
4214
1593
103
196
Belgium
1152
537
3838
1535
230
384
AS ankylosing spondylitis, CD Crohn’s disease, PsA psoriatic arthritis, RA rheumatoid arthritis, UC ulcerative colitis
aPharmapoint Rheumatoid Arthritis Global Forecast 2013–2022. Data on file. Values for Netherlands and Belgium were taken from a Western Europe average of France, Germany and United Kingdom treatment data
bRA data used as proxy
cIMS 2013. Data on file
The number of patients calculated through this approach in the model received either Remicade or Remsima, according to the market uptake assumptions made.
Uptake of Remsima
The uptake of Remsima (expressed as the proportion of patients receiving Remsima who would otherwise have received Remicade) was estimated at 25% in the switch and 50% in the naïve populations. The difference in values was adopted to reflect that uptake is likely to be greater in treatment-naïve patients compared with patients who could potentially switch, because patients already receiving Remicade might be more likely to stay on their existing therapy compared with those initiating infliximab therapy. In our model, there was a linear relation between uptake and budget impact (i.e., doubling the uptake from 50% to 100% would double the budget impact). Therefore, the impact of changes in uptake could be easily inferred, but has not been investigated in a sensitivity analysis.
Costs
The country-specific list prices for Remicade used in the model are shown in Table 1. Remsima had not launched at the time of model development, and the exact local price of Remicade was not known, because biologics are often discounted at a local level. Therefore, this model was built with a range of discount scenarios (10–30%, assumption) compared with the current list price of Remicade.
Dosing was assumed to be the same for Remicade and Remsima, and was taken from the Remicade Summary of Product Characteristics [21] (Table 2). Treatment-naïve patients (but not switch patients) were assumed to receive a loading-dose phase. The loading dose was equivalent to the maintenance dose, except for a shorter time interval between loading doses than between subsequent maintenance doses. It was conservatively assumed that vials would be shared in the most-efficient manner. Only direct drug costs were considered in the model. All other costs (e.g., the cost of administration, monitoring, and adverse events) were assumed to be the same for Remicade and Remsima [30].
The analysis in this article was based on previously conducted studies, and did not involve any new studies of human or animal subjects performed by any of the authors.
Model Structure and Equations
Patient Numbers
The total number of patients being treated with either Remsima or Remicade was defined as:
$$ \rho \; = \alpha + \beta $$
where \( \rho \) is total number of patients (treated with either Remicade or Remsima); \( \alpha \) is number of patients treated with Remicade in the model; \( \beta \) is number of patients treated with Remsima in the model.
The variables \( \alpha \) and \( \beta \) were calculated as follows:
where \( i \) is countries selected in the model; \( j \) is indications selected in the model; \( p_{ij} \) is total population of indication \( j \) in country \( i \); \( a_{ij} \) for switch patient group: prevalence of indication \( j \) in country \( i \), for treatment-naïve patient group: incidence of indication \( j \) in country \( i \) (Table 2); \( b_{ij} \) is proportion of patients treated with drugs for indication \( j \) in country \( i \); \( c_{ij} \) is proportion of drug-treated patients treated with Remsima indication \( j \) in country \( i \).
For the purpose of this budget impact model, it was assumed that the total patients \( \rho \) was constant in both scenarios (introducing Remsima or not introducing it), that is, patients switching to Remsima always did so from Remicade. This assumption was made to enable direct comparison of cost difference between the two scenarios.
where \( \gamma \) = total cost per Remicade patient for indication \( j \) in country \( i \); \( \delta \) is total cost per Remsima patient for indication \( j \) in country \( i \); \( g_{i} \) is cost per 100-mg vial of Remicade in country \( i \); \( h_{i} \) is cost per 100-mg vial of Remsima in country \( i \); \( z_{j} \) is total number of vials required per patient per dose for indication \( j \)\( \left[ {{\text{calculated\, as}}\frac{{\left( {{\text{mg\, per\, kg}}\; [ {\text{as\, defined\, in\, SPC]}}} \right)}}{100}{ \times }({\text{average\, patient\, weight}})} \right] \); \( j_{j} \) for naïve patients: total number of doses required per year for indication \( j \): Table 2, calculated as: \( \frac{{52 - ({\text{time\, interval \, from \, initial \, dose \, to \, maintenance \, phase}})}}{{({\text{number \, of \, weeks \, between \, maintenance \, doses}})}} + 3 \), where 3 represented the loading doses (i.e., the doses until maintenance intervals were established), for switch patients: total number of doses required per year for indication \( j \): calculated as: \( \frac{{ 52 \ {\text{weeks}}}}{{\left( {\text{number \ of \ weeks \ between \ doses } [\text{as \ defined \ in \ SPC}]} \right)}}. \)
Sensitivity analyses were conducted to assess the robustness of results. Parameters varied in the sensitivity analysis included the number of patients treated with Remicade (±10%), prevalence estimates (±10%), incidence estimates (±10%), and patient’s weight (±5 kg). Parameters were varied for both the ‘switch’ and naïve population groups within the specified ranges for each of the indications of interest. The analyses were performed for each of the three discount scenarios.
Anzeige
Results
Assuming that Remsima would be available at a price that is between 10% and 30% less than that of Remicade, the annual drug cost savings that could be made through the introduction of Remsima across the six licensed disease areas were projected to range from €2.89 million in Belgium (10% discount scenario) to €33.80 million in Germany (30% discount scenario) (Table 4) (for infliximab-naïve and switch patients combined). The cumulative drug cost savings across the five countries included (Germany, the UK, Italy, the Netherlands, and Belgium) and the six licensed disease areas were projected to range from €25.79 million (10% discount) to €77.37 million (30% discount). Detailed projected drug cost savings by disease area and country are shown in Table 4. If such savings were made and used to treat additional patients with Remsima, the number of additional patients that could be treated across the six disease areas ranged from 250 in Belgium (10% discount scenario) to 2602 in Germany (30% discount scenario) (Table 5). Detailed results for estimated numbers of additional patients that could be treated with Remsima are shown in Table 5.
Table 4
Projected drug cost savings resulting from the introduction of Remsima during the first year after launch; combined for switch and naïve patient populations
Million €a
RA
AS
CD
UC
PsA
Psoriasis
Total
10% discount scenario
Germany
0.575
0.811
5.969
2.112
1.241
0.558
11.266
UK
0.597
0.190
2.118
0.327
0.185
0.205
3.621
Italy
0.646
0.677
0.734
0.932
0.967
0.670
4.625
The Netherlands
0.257
0.235
1.784
0.967
0.101
0.044
3.389
Belgium
0.240
0.237
1.343
0.810
0.173
0.085
2.887
Total
2.315
2.150
11.949
5.148
2.667
1.561
25.789
20% discount scenario
Germany
1.149
1.623
11.939
4.225
2.481
1.117
22.532
UK
1.194
0.380
4.235
0.654
0.370
0.409
7.242
Italy
1.291
1.355
1.469
1.863
1.935
1.339
9.252
The Netherlands
0.515
0.471
3.569
1.934
0.203
0.087
6.778
Belgium
0.480
0.474
2.686
1.621
0.345
0.169
5.775
Total
4.630
4.301
23.897
10.295
5.333
3.121
51.578
30% discount scenario
Germany
1.724
2.432
17.908
6.337
3.722
1.675
33.798
UK
1.792
0.569
6.353
0.980
0.554
0.614
10.862
Italy
1.937
2.032
2.203
2.795
2.902
2.009
13.878
The Netherlands
0.772
0.706
5.353
2.900
0.304
0.131
10.167
Belgium
0.720
0.711
4.028
2.431
0.518
0.254
8.662
Total
6.944
6.451
35.846
15.443
8.000
4.682
77.367
Numbers have been rounded to the nearest 10,000
AS ankylosing spondylitis, CD Crohn’s disease, PsA psoriatic arthritis, RA rheumatoid arthritis, UC ulcerative colitis
Number of additional patients who could be treated with Remsima using the drug cost savings made during the first year after launch of Remsima; combined for switch and naïve patient populations
RA
AS
CD
UC
PsA
Psoriasis
Total
10% discount scenario
Germany
57
41
352
122
69
33
674
UK
94
15
197
30
16
19
372
Italy
84
50
64
79
79
54
410
The Netherlands
32
15
130
66
7
3
253
Belgium
34
17
114
63
14
7
250
Total
300
139
858
361
186
116
1960
20% discount scenario
Germany
128
93
792
275
156
74
1517
UK
211
35
444
69
37
42
838
Italy
189
113
144
178
178
121
924
The Netherlands
71
34
293
148
16
7
570
Belgium
77
39
257
142
31
16
562
Total
676
313
1,930
812
419
260
4410
30% discount scenario
Germany
219
159
1358
472
268
126
2602
UK
362
60
762
117
64
72
1436
Italy
324
195
247
305
306
208
1583
The Netherlands
122
58
503
253
27
12
976
Belgium
132
67
440
244
54
27
964
Total
1158
538
3309
1392
718
446
7561
Numbers of patients have been rounded to the nearest integer
AS ankylosing spondylitis, CD Crohn’s disease, PsA psoriatic arthritis, RA rheumatoid arthritis, UC ulcerative colitis
Sensitivity Analyses
Tornado diagrams for the one-way sensitivity analyses are shown in Fig. 1 (for the 10% discount scenario), Fig. 2 (for the 20% discount scenario), and Fig. 3 (for the 30% discount scenario). As would be expected, any changes have the lowest impact in the 10% discount scenario and the highest impact in the 30% discount scenario. Of the four parameters explored in the sensitivity analysis, the percentage of patients treated with Remicade (i.e., the total number of patients considered in the model) had the biggest impact, because an increase or decrease in this parameter would translate directly and linearly into the projected savings (i.e., a 10% increase in patients being treated with Remicade or Remsima led to a 10% increase in projected savings, if all other model parameters remained unchanged). The impact of a change in prevalence was slightly lower, with a 10% change leading to a corresponding 8.4% change in projected savings. Changing patient weight by 5 kg led to a change in projected savings of 6.7%. A 10% change in disease incidence had the smallest impact, with only a 1.6% change in projected savings.
Fig. 1
Sensitivity analyses of projected drug cost savings resulting from the introduction of Remsima; 10% discount scenario. M million
Fig. 2
Sensitivity analyses of projected drug cost savings resulting from the introduction of Remsima; 20% discount scenario. M million
Fig. 3
Sensitivity analyses of projected drug cost savings due to the introduction of Remsima; 30% discount scenario. M million
×
×
×
Discussion
We developed a budget impact model for the introduction of Remsima in five European countries over a 1-year time horizon. The list price of Remsima was not known at the time of this analysis. This budget impact model was based on the assumption that the list price of Remsima might be between 10% and 30% lower than the current list price of Remicade. Our model showed that the introduction of Remsima under those circumstances was highly likely to be associated with considerable drug cost savings for the healthcare payer. Our model found the price of Remsima to be the main driver of budget impact (as demonstrated by the different price-discount scenarios). The number of patients currently treated with Remicade was found to have a considerable, but less important, directly correlating effect on the projected savings. Changes in prevalence and patient weight had slightly less impact on projected savings. Changes in incidence were found to lead to the lowest changes in budget impact (among the variables explored).
The analysis is limited by the fact that the final launch price of Remsima and local discounts of Remsima and Remicade, which our model showed to be the main determinant of the budget impact, is not yet known. We also emphasize the importance of local price negotiations, which might have a significant effect on the budget impact. Furthermore, this analysis assumed the same administration and monitoring cost for Remsima and Remicade and the model did not take patient mortality into account, which introduces a slight bias that might overstate the budget impact of Remsima.
Anzeige
Since the development of our model, Remsima has launched in the five countries included in the analysis. Based on the 2015 list prices of Remsima and Remicade, the introduction of Remsima would lead to budget savings of €45.13 million and 3900 additional patients could be treated with Remsima across the five countries included. Appendix B provides the results of this additional analysis (Appendix B). However, the range of price discounts in the main analysis remains valid, given the uncertainty around local discounts provided for both therapies and possible price changes. Therefore, these results need to be interpreted with caution.
The results of our budget impact model strongly suggested that, if decision makers facilitated access to Remsima, potential drug cost savings could be made. Furthermore, there are indicators (based on UK data collected in 2006) that, because of the high drug-acquisition cost, not all patients who could benefit from anti-TNF therapy have access to it [49]. If this is the case, our analysis showed that there is the potential for additional patients to be treated with Remsima.
Conclusion
The introduction of Remsima could lead to drug cost-related savings across Germany, the UK, Italy, the Netherlands, and Belgium. A less-costly brand of infliximab might also lead to wider patient access and, therefore, improved patient outcomes.
Acknowledgments
Sponsorship for this study and article-processing charges, as well as the open access fee, were funded by Mundipharma International Ltd, Cambridge, UK, which also commissioned and funded the study. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval to the version to be published. The manuscript was prepared by Brigitte Moore, of Abacus International, and funded by Mundipharma International Ld, Cambridge, UK.
Anzeige
Conflict of interest
Ashok Jha and Will Dunlop are employees of Mundipharma International Ltd, Cambridge, UK. Alex Upton is an employee of Abacus International, Bicester, UK, which was contracted by Mundipharma International Ltd. Ron Akehurst has previously received fees from Mundipharma International Ltd for consulting services.
Compliance with ethics guidelines
The analysis in this article was based on previously conducted studies, and did not involve any new studies of human or animal subjects performed by any of the authors.
Open Access
This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0), which permits use, duplication, adaptation, distribution, and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
Mit e.Med Innere Medizin erhalten Sie Zugang zu CME-Fortbildungen des Fachgebietes Innere Medizin, den Premium-Inhalten der internistischen Fachzeitschriften, inklusive einer gedruckten internistischen Zeitschrift Ihrer Wahl.
Mit e.Med Allgemeinmedizin erhalten Sie Zugang zu allen CME-Fortbildungen und Premium-Inhalten der allgemeinmedizinischen Zeitschriften, inklusive einer gedruckten Allgemeinmedizin-Zeitschrift Ihrer Wahl.
Immunchemischer Stuhltest positiv, Koloskopie negativ – in solchen Fällen kann die Blutungsquelle auch weiter proximal sitzen. Ein Forschungsteam hat nachgesehen, wie häufig und in welchen Lokalisationen das der Fall ist.
Möglicherweise hängt es von der Art der Diabetesmedikamente ab, wie hoch das Risiko der Betroffenen ist, dass sich sehkraftgefährdende Komplikationen verschlimmern.
In der MONARCHE-3-Studie lebten Frauen mit fortgeschrittenem Hormonrezeptor-positivem, HER2-negativem Brustkrebs länger, wenn sie zusätzlich zu einem nicht steroidalen Aromatasehemmer mit Abemaciclib behandelt wurden; allerdings verfehlte der numerische Zugewinn die statistische Signifikanz.
Welchen Nutzen es trägt, wenn die Strahlentherapie nach radikaler Prostatektomie um eine Androgendeprivation ergänzt wird, hat die RADICALS-HD-Studie untersucht. Nun liegen die Ergebnisse vor. Sie sprechen für länger dauernden Hormonentzug.
Update Innere Medizin
Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.
