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Erschienen in: Clinical Drug Investigation 10/2017

01.10.2017 | Review Article

Novel Biologic Agents Targeting Interleukin-23 and Interleukin-17 for Moderate-to-Severe Psoriasis

verfasst von: Zeyu Chen, Yu Gong, Yuling Shi

Erschienen in: Clinical Drug Investigation | Ausgabe 10/2017

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Abstract

Psoriasis is a common, chronic inflammatory skin disease and cannot be cured. The treatment of moderate-to-severe plaque psoriasis has been revolutionized with the development of biologic agents for nearly 20 years. Current studies show that interleukin-23 and interleukin-17 play remarkable roles in the pathogenesis of psoriasis. Interleukin-23 can sustain the differentiation and maintenance of T helper-17 lineage. Interleukin-17 can recruit and stimulate many cells, which play important parts in psoriasis through interacting with the interleukin-17 receptor. Several biologic agents targeting interleukin-23, interleukin-17, or their receptors are now in different stages: some are approved or clinical trials are in progress. Ustekinumab targets interleukin-23/interleukin-12p40; risankizumab, guselkumab, and tildrakizumab target interleukin-23p19; secukinumab and ixekizumab target interleukin-17A; and brodalumab targets the interleukin-17 receptors. All of these agents have good efficacy in treating moderate-to-severe psoriasis.
Literatur
2.
Zurück zum Zitat Ding X, Wang T, Shen Y, Wang X, Zhou C, Tian S, et al. Prevalence of psoriasis in China: a population-based study in six cities. Eur J Dermatol. 2012;22(5):663–7. doi:10.1684/ejd.2012.1802.PubMed Ding X, Wang T, Shen Y, Wang X, Zhou C, Tian S, et al. Prevalence of psoriasis in China: a population-based study in six cities. Eur J Dermatol. 2012;22(5):663–7. doi:10.​1684/​ejd.​2012.​1802.PubMed
4.
Zurück zum Zitat Lebwohl MG, Bachelez H, Barker J, Girolomoni G, Kavanaugh A, Langley RG, et al. Patient perspectives in the management of psoriasis: results from the population-based Multinational Assessment of Psoriasis and Psoriatic Arthritis Survey. J Am Acad Dermatol. 2014;70(5):871–881.e1-30. doi:10.1016/j.jaad.2013.12.018.CrossRefPubMed Lebwohl MG, Bachelez H, Barker J, Girolomoni G, Kavanaugh A, Langley RG, et al. Patient perspectives in the management of psoriasis: results from the population-based Multinational Assessment of Psoriasis and Psoriatic Arthritis Survey. J Am Acad Dermatol. 2014;70(5):871–881.e1-30. doi:10.​1016/​j.​jaad.​2013.​12.​018.CrossRefPubMed
5.
Zurück zum Zitat Teng MW, Bowman EP, McElwee JJ, Smyth MJ, Casanova JL, Cooper AM, et al. IL-12 and IL-23 cytokines: from discovery to targeted therapies for immune-mediated inflammatory diseases. Nat Med. 2015;21(7):719–29. doi:10.1038/nm.3895.CrossRefPubMed Teng MW, Bowman EP, McElwee JJ, Smyth MJ, Casanova JL, Cooper AM, et al. IL-12 and IL-23 cytokines: from discovery to targeted therapies for immune-mediated inflammatory diseases. Nat Med. 2015;21(7):719–29. doi:10.​1038/​nm.​3895.CrossRefPubMed
7.
Zurück zum Zitat McGeachy MJ, Chen Y, Tato CM, Laurence A, Joyce-Shaikh B, Blumenschein WM, et al. The interleukin 23 receptor is essential for the terminal differentiation of interleukin 17-producing effector T helper cells in vivo. Nat Immunol. 2009;10(3):314–24. doi:10.1038/ni.1698.CrossRefPubMedPubMedCentral McGeachy MJ, Chen Y, Tato CM, Laurence A, Joyce-Shaikh B, Blumenschein WM, et al. The interleukin 23 receptor is essential for the terminal differentiation of interleukin 17-producing effector T helper cells in vivo. Nat Immunol. 2009;10(3):314–24. doi:10.​1038/​ni.​1698.CrossRefPubMedPubMedCentral
8.
Zurück zum Zitat Umezawa Y, Nakagawa H, Niiro H, Ootaki K. Long-term clinical safety and efficacy of brodalumab in the treatment of Japanese patients with moderate-to-severe plaque psoriasis. J Eur Acad Dermatol Venereol. 2016;30(11):1957–60. doi:10.1111/jdv.13785.PubMed Umezawa Y, Nakagawa H, Niiro H, Ootaki K. Long-term clinical safety and efficacy of brodalumab in the treatment of Japanese patients with moderate-to-severe plaque psoriasis. J Eur Acad Dermatol Venereol. 2016;30(11):1957–60. doi:10.​1111/​jdv.​13785.PubMed
10.
Zurück zum Zitat Farahnik B, Beroukhim K, Abrouk M, Nakamura M, Zhu TH, Singh R, et al. Brodalumab for the treatment of psoriasis: a review of phase III trials. Dermatol Ther. 2016;6(2):111–24. doi:10.1007/s13555-016-0121-x.CrossRef Farahnik B, Beroukhim K, Abrouk M, Nakamura M, Zhu TH, Singh R, et al. Brodalumab for the treatment of psoriasis: a review of phase III trials. Dermatol Ther. 2016;6(2):111–24. doi:10.​1007/​s13555-016-0121-x.CrossRef
11.
Zurück zum Zitat Leonardi CL, Kimball AB, Papp KA, Yeilding N, Guzzo C, Wang Y, et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 1). Lancet. 2008;371(9625):1665–74. doi:10.1016/s0140-6736(08)60725-4.CrossRefPubMed Leonardi CL, Kimball AB, Papp KA, Yeilding N, Guzzo C, Wang Y, et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 1). Lancet. 2008;371(9625):1665–74. doi:10.​1016/​s0140-6736(08)60725-4.CrossRefPubMed
12.
Zurück zum Zitat Papp KA, Langley RG, Lebwohl M, Krueger GG, Szapary P, Yeilding N, et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2). Lancet. 2008;371(9625):1675–84. doi:10.1016/s0140-6736(08)60726-6.CrossRefPubMed Papp KA, Langley RG, Lebwohl M, Krueger GG, Szapary P, Yeilding N, et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2). Lancet. 2008;371(9625):1675–84. doi:10.​1016/​s0140-6736(08)60726-6.CrossRefPubMed
13.
Zurück zum Zitat Kimball AB, Papp KA, Wasfi Y, Chan D, Bissonnette R, Sofen H, et al. Long-term efficacy of ustekinumab in patients with moderate-to-severe psoriasis treated for up to 5 years in the PHOENIX 1 study. J Eur Acad Dermatol Venereol. 2013;27(12):1535–45. doi:10.1111/jdv.12046.CrossRefPubMed Kimball AB, Papp KA, Wasfi Y, Chan D, Bissonnette R, Sofen H, et al. Long-term efficacy of ustekinumab in patients with moderate-to-severe psoriasis treated for up to 5 years in the PHOENIX 1 study. J Eur Acad Dermatol Venereol. 2013;27(12):1535–45. doi:10.​1111/​jdv.​12046.CrossRefPubMed
14.
Zurück zum Zitat Langley RG, Lebwohl M, Krueger GG, Szapary PO, Wasfi Y, Chan D, et al. Long-term efficacy and safety of ustekinumab, with and without dosing adjustment, in patients with moderate-to-severe psoriasis: results from the PHOENIX 2 study through 5 years of follow-up. Br J Dermatol. 2015;172(5):1371–83. doi:10.1111/bjd.13469.CrossRefPubMed Langley RG, Lebwohl M, Krueger GG, Szapary PO, Wasfi Y, Chan D, et al. Long-term efficacy and safety of ustekinumab, with and without dosing adjustment, in patients with moderate-to-severe psoriasis: results from the PHOENIX 2 study through 5 years of follow-up. Br J Dermatol. 2015;172(5):1371–83. doi:10.​1111/​bjd.​13469.CrossRefPubMed
15.
Zurück zum Zitat Augustin M, Blome C, Paul C, Puig L, Luger T, Lambert J, et al. Quality of life and patient benefit following transition from methotrexate to ustekinumab in psoriasis. J Eur Acad Dermatol Venereol. 2017;31(2):294–303. doi:10.1111/jdv.13823.CrossRefPubMed Augustin M, Blome C, Paul C, Puig L, Luger T, Lambert J, et al. Quality of life and patient benefit following transition from methotrexate to ustekinumab in psoriasis. J Eur Acad Dermatol Venereol. 2017;31(2):294–303. doi:10.​1111/​jdv.​13823.CrossRefPubMed
16.
Zurück zum Zitat Takahashi N, Noda S, Taniguchi T, Adachi M. Efficacy comparison of ustekinumab between anti-tumor necrosis factor-alpha drug-naive and anti-tumor necrosis factor-alpha drug-resistant Japanese psoriasis cases. Int J Dermatol. 2015;54(10):1194–8. doi:10.1111/ijd.12859.CrossRefPubMed Takahashi N, Noda S, Taniguchi T, Adachi M. Efficacy comparison of ustekinumab between anti-tumor necrosis factor-alpha drug-naive and anti-tumor necrosis factor-alpha drug-resistant Japanese psoriasis cases. Int J Dermatol. 2015;54(10):1194–8. doi:10.​1111/​ijd.​12859.CrossRefPubMed
17.
Zurück zum Zitat Landells I, Marano C, Hsu MC, Li S, Zhu Y, Eichenfield LF, et al. Ustekinumab in adolescent patients age 12 to 17 years with moderate-to-severe plaque psoriasis: results of the randomized phase 3 CADMUS study. J Am Acad Dermatol. 2015;73(4):594–603. doi:10.1016/j.jaad.2015.07.002.CrossRefPubMed Landells I, Marano C, Hsu MC, Li S, Zhu Y, Eichenfield LF, et al. Ustekinumab in adolescent patients age 12 to 17 years with moderate-to-severe plaque psoriasis: results of the randomized phase 3 CADMUS study. J Am Acad Dermatol. 2015;73(4):594–603. doi:10.​1016/​j.​jaad.​2015.​07.​002.CrossRefPubMed
18.
Zurück zum Zitat Onderdijk AJ, Ijpma AS, Menting SP, Baerveldt EM, Prens EP. Potential serum biomarkers of treatment response to ustekinumab in patients with psoriasis: a pilot study. Br J Dermatol. 2015;173(6):1536–9. doi:10.1111/bjd.13997.CrossRefPubMed Onderdijk AJ, Ijpma AS, Menting SP, Baerveldt EM, Prens EP. Potential serum biomarkers of treatment response to ustekinumab in patients with psoriasis: a pilot study. Br J Dermatol. 2015;173(6):1536–9. doi:10.​1111/​bjd.​13997.CrossRefPubMed
19.
Zurück zum Zitat Reich K, Papp KA, Blauvelt A, Tyring SK, Sinclair R, Thaci D, et al. Tildrakizumab versus placebo or etanercept for chronic plaque psoriasis (reSURFACE 1 and reSURFACE 2): results from two randomised controlled, phase 3 trials. Lancet. 2017;. doi:10.1016/s0140-6736(17)31279-5 (pii: S0140-6736(17)31279-5). Reich K, Papp KA, Blauvelt A, Tyring SK, Sinclair R, Thaci D, et al. Tildrakizumab versus placebo or etanercept for chronic plaque psoriasis (reSURFACE 1 and reSURFACE 2): results from two randomised controlled, phase 3 trials. Lancet. 2017;. doi:10.​1016/​s0140-6736(17)31279-5 (pii: S0140-6736(17)31279-5).
20.
Zurück zum Zitat Papp K, Thaci D, Reich K, Riedl E, Langley RG, Krueger JG, et al. Tildrakizumab (MK-3222), an anti-interleukin-23p19 monoclonal antibody, improves psoriasis in a phase IIb randomized placebo-controlled trial. Br J Dermatol. 2015;173(4):930–9. doi:10.1111/bjd.13932.CrossRefPubMed Papp K, Thaci D, Reich K, Riedl E, Langley RG, Krueger JG, et al. Tildrakizumab (MK-3222), an anti-interleukin-23p19 monoclonal antibody, improves psoriasis in a phase IIb randomized placebo-controlled trial. Br J Dermatol. 2015;173(4):930–9. doi:10.​1111/​bjd.​13932.CrossRefPubMed
21.
Zurück zum Zitat Langley RG, Tsai TF, Flavin S, Song M, Randazzo B, Wasfi Y, et al. Efficacy and safety of guselkumab in patients with psoriasis who have an inadequate response to ustekinumab: results of the randomized, double-blind, phase 3 NAVIGATE trial. Br J Dermatol. 2017;. doi:10.1111/bjd.15750. Langley RG, Tsai TF, Flavin S, Song M, Randazzo B, Wasfi Y, et al. Efficacy and safety of guselkumab in patients with psoriasis who have an inadequate response to ustekinumab: results of the randomized, double-blind, phase 3 NAVIGATE trial. Br J Dermatol. 2017;. doi:10.​1111/​bjd.​15750.
22.
Zurück zum Zitat Reich K, Armstrong AW, Foley P, Song M, Wasfi Y, Randazzo B, et al. Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the treatment of patients with moderate to severe psoriasis with randomized withdrawal and retreatment: results from the phase III, double-blind, placebo- and active comparator-controlled VOYAGE 2 trial. J Am Acad Dermatol. 2017;76(3):418–31. doi:10.1016/j.jaad.2016.11.042.CrossRefPubMed Reich K, Armstrong AW, Foley P, Song M, Wasfi Y, Randazzo B, et al. Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the treatment of patients with moderate to severe psoriasis with randomized withdrawal and retreatment: results from the phase III, double-blind, placebo- and active comparator-controlled VOYAGE 2 trial. J Am Acad Dermatol. 2017;76(3):418–31. doi:10.​1016/​j.​jaad.​2016.​11.​042.CrossRefPubMed
23.
Zurück zum Zitat Blauvelt A, Papp KA, Griffiths CE, Randazzo B, Wasfi Y, Shen YK, et al. Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the continuous treatment of patients with moderate to severe psoriasis: results from the phase III, double-blinded, placebo- and active comparator-controlled VOYAGE 1 trial. J Am Acad Dermatol. 2017;76(3):405–17. doi:10.1016/j.jaad.2016.11.041.CrossRefPubMed Blauvelt A, Papp KA, Griffiths CE, Randazzo B, Wasfi Y, Shen YK, et al. Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the continuous treatment of patients with moderate to severe psoriasis: results from the phase III, double-blinded, placebo- and active comparator-controlled VOYAGE 1 trial. J Am Acad Dermatol. 2017;76(3):405–17. doi:10.​1016/​j.​jaad.​2016.​11.​041.CrossRefPubMed
24.
Zurück zum Zitat Papp KA, Blauvelt A, Bukhalo M, Gooderham M, Krueger JG, Lacour JP, et al. Risankizumab versus ustekinumab for moderate-to-severe plaque psoriasis. N Engl J Med. 2017;376(16):1551–60. doi:10.1056/NEJMoa1607017.CrossRefPubMed Papp KA, Blauvelt A, Bukhalo M, Gooderham M, Krueger JG, Lacour JP, et al. Risankizumab versus ustekinumab for moderate-to-severe plaque psoriasis. N Engl J Med. 2017;376(16):1551–60. doi:10.​1056/​NEJMoa1607017.CrossRefPubMed
25.
Zurück zum Zitat Papp K, Menter A, Sofen H, Tyring S, Lacour JP, Berner B, et al. Efficacy and safety of different dose regimens of a selective IL-23p19 inhibitor (BI 655066) compared with ustekinumab in patients with moderate-to-severe plaque psoriasis with and without psoriatic arthritis. Arthritis Rheumatol. 2015;67:2569–70.CrossRef Papp K, Menter A, Sofen H, Tyring S, Lacour JP, Berner B, et al. Efficacy and safety of different dose regimens of a selective IL-23p19 inhibitor (BI 655066) compared with ustekinumab in patients with moderate-to-severe plaque psoriasis with and without psoriatic arthritis. Arthritis Rheumatol. 2015;67:2569–70.CrossRef
27.
Zurück zum Zitat Russell CB, Rand H, Bigler J, Kerkof K, Timour M, Bautista E, et al. Gene expression profiles normalized in psoriatic skin by treatment with brodalumab, a human anti-IL-17 receptor monoclonal antibody. J Immunol. 2014;192(8):3828–36. doi:10.4049/jimmunol.1301737.CrossRefPubMed Russell CB, Rand H, Bigler J, Kerkof K, Timour M, Bautista E, et al. Gene expression profiles normalized in psoriatic skin by treatment with brodalumab, a human anti-IL-17 receptor monoclonal antibody. J Immunol. 2014;192(8):3828–36. doi:10.​4049/​jimmunol.​1301737.CrossRefPubMed
28.
29.
Zurück zum Zitat Foley P. Brodalumab, an anti-IL17RA monoclonal antibody, in psoriatic arthritis. N Engl J Med. 2014;370(24):2295–306.CrossRef Foley P. Brodalumab, an anti-IL17RA monoclonal antibody, in psoriatic arthritis. N Engl J Med. 2014;370(24):2295–306.CrossRef
30.
Zurück zum Zitat Farahnik B, Beroukhim K, Nakamura M, Abrouk M, Zhu TH, Singh R, et al. Anti-IL-17 agents for psoriasis: a review of phase III data. J Drugs Dermatol. 2016;15(3):311–6.PubMed Farahnik B, Beroukhim K, Nakamura M, Abrouk M, Zhu TH, Singh R, et al. Anti-IL-17 agents for psoriasis: a review of phase III data. J Drugs Dermatol. 2016;15(3):311–6.PubMed
31.
32.
Zurück zum Zitat Blauvelt A, Prinz JC, Gottlieb AB, Kingo K, Sofen H, Ruer-Mulard M, et al. Secukinumab administration by pre-filled syringe: efficacy, safety and usability results from a randomized controlled trial in psoriasis (FEATURE). Br J Dermatol. 2015;172(2):484–93. doi:10.1111/bjd.13348.CrossRefPubMed Blauvelt A, Prinz JC, Gottlieb AB, Kingo K, Sofen H, Ruer-Mulard M, et al. Secukinumab administration by pre-filled syringe: efficacy, safety and usability results from a randomized controlled trial in psoriasis (FEATURE). Br J Dermatol. 2015;172(2):484–93. doi:10.​1111/​bjd.​13348.CrossRefPubMed
33.
Zurück zum Zitat Paul C, Lacour JP, Tedremets L, Kreutzer K, Jazayeri S, Adams S, et al. Efficacy, safety and usability of secukinumab administration by autoinjector/pen in psoriasis: a randomized, controlled trial (JUNCTURE). J Eur Acad Dermatol Venereol. 2015;29(6):1082–90. doi:10.1111/jdv.12751.CrossRefPubMed Paul C, Lacour JP, Tedremets L, Kreutzer K, Jazayeri S, Adams S, et al. Efficacy, safety and usability of secukinumab administration by autoinjector/pen in psoriasis: a randomized, controlled trial (JUNCTURE). J Eur Acad Dermatol Venereol. 2015;29(6):1082–90. doi:10.​1111/​jdv.​12751.CrossRefPubMed
34.
Zurück zum Zitat Mrowietz U, Leonardi CL, Girolomoni G, Toth D, Morita A, Balki SA, et al. Secukinumab retreatment-as-needed versus fixed-interval maintenance regimen for moderate to severe plaque psoriasis: a randomized, double-blind, noninferiority trial (SCULPTURE). J Am Acad Dermatol. 2015;73(1):27–36.e1. doi:10.1016/j.jaad.2015.04.011.CrossRefPubMed Mrowietz U, Leonardi CL, Girolomoni G, Toth D, Morita A, Balki SA, et al. Secukinumab retreatment-as-needed versus fixed-interval maintenance regimen for moderate to severe plaque psoriasis: a randomized, double-blind, noninferiority trial (SCULPTURE). J Am Acad Dermatol. 2015;73(1):27–36.e1. doi:10.​1016/​j.​jaad.​2015.​04.​011.CrossRefPubMed
36.
Zurück zum Zitat van de Kerkhof PC, Griffiths CE, Reich K, Leonardi CL, Blauvelt A, Tsai TF, et al. Secukinumab long-term safety experience: a pooled analysis of 10 phase II and III clinical studies in patients with moderate to severe plaque psoriasis. J Am Acad Dermatol. 2016;75(1):83–98.e4. doi:10.1016/j.jaad.2016.03.024.CrossRefPubMed van de Kerkhof PC, Griffiths CE, Reich K, Leonardi CL, Blauvelt A, Tsai TF, et al. Secukinumab long-term safety experience: a pooled analysis of 10 phase II and III clinical studies in patients with moderate to severe plaque psoriasis. J Am Acad Dermatol. 2016;75(1):83–98.e4. doi:10.​1016/​j.​jaad.​2016.​03.​024.CrossRefPubMed
37.
38.
Zurück zum Zitat Griffiths CE, Reich K, Lebwohl M, van de Kerkhof P, Paul C, Menter A, et al. Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis (UNCOVER-2 and UNCOVER-3): results from two phase 3 randomised trials. Lancet. 2015;386(9993):541–51. doi:10.1016/s0140-6736(15)60125-8.CrossRefPubMed Griffiths CE, Reich K, Lebwohl M, van de Kerkhof P, Paul C, Menter A, et al. Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis (UNCOVER-2 and UNCOVER-3): results from two phase 3 randomised trials. Lancet. 2015;386(9993):541–51. doi:10.​1016/​s0140-6736(15)60125-8.CrossRefPubMed
39.
Zurück zum Zitat Glatt S, Helmer E, Haier B, Strimenopoulou F, Price G, Vajjah P, et al. First-in-human randomized study of bimekizumab, a humanized monoclonal antibody and selective dual inhibitor of IL-17A and IL-17F, in mild psoriasis. Br J Clin Pharmacol. 2017;83(5):991–1001. doi:10.1111/bcp.13185.CrossRefPubMedPubMedCentral Glatt S, Helmer E, Haier B, Strimenopoulou F, Price G, Vajjah P, et al. First-in-human randomized study of bimekizumab, a humanized monoclonal antibody and selective dual inhibitor of IL-17A and IL-17F, in mild psoriasis. Br J Clin Pharmacol. 2017;83(5):991–1001. doi:10.​1111/​bcp.​13185.CrossRefPubMedPubMedCentral
41.
Zurück zum Zitat Ayala F, Lambert J. Efficacy, tolerability and safety of switching from etanercept to infliximab for the treatment of moderate-to-severe psoriasis: a multicenter, open-label trial (TANGO). J Dermatol Treat. 2015;26(4):304–11. doi:10.3109/09546634.2014.952611.CrossRef Ayala F, Lambert J. Efficacy, tolerability and safety of switching from etanercept to infliximab for the treatment of moderate-to-severe psoriasis: a multicenter, open-label trial (TANGO). J Dermatol Treat. 2015;26(4):304–11. doi:10.​3109/​09546634.​2014.​952611.CrossRef
Metadaten
Titel
Novel Biologic Agents Targeting Interleukin-23 and Interleukin-17 for Moderate-to-Severe Psoriasis
verfasst von
Zeyu Chen
Yu Gong
Yuling Shi
Publikationsdatum
01.10.2017
Verlag
Springer International Publishing
Erschienen in
Clinical Drug Investigation / Ausgabe 10/2017
Print ISSN: 1173-2563
Elektronische ISSN: 1179-1918
DOI
https://doi.org/10.1007/s40261-017-0550-z

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