Detailed Long-term Dynamics of Neutrophil-to-Lymphocyte Ratio under Biologic Treatment Reveal Differential Effects of Tumour Necrosis Factor-alpha and Interleukin 12/23 Antagonists

Authors

  • Jochen H. O. Hoffmann Department of Dermatology, University of Heidelberg, INF 440, DE-69120 Heidelberg, Germany
  • Christian Knoop
  • Alexander H. Enk
  • Eva N. Hadaschik

DOI:

https://doi.org/10.2340/actadv.v101.271

Keywords:

adalimumab, etanercept, ustekinumab, biomarker, cardiovascular disease, psoriasis

Abstract

Psoriasis is thought to be associated with a reduced life expectancy through systemic inflammation. A comparative, retrospective analysis of neutrophil-to-lympho-cyte ratio, a biomarker of systemic inflammation and cardiovascular risk, under 196 treatments with tumour necrosis factor-α and interleukin-12/23 antagonists was performed. Neutrophil-to-lympho-cyte ratio decreased significantly within 3 months of initiation of treatment and remained stable at reduced levels for at least 33 months. Dynamics were more pronounced and neutrophil-to-lympho-cyte ratio under treatment was lower in patients treated with tumour necrosis factor-α compared with interleukin-12/23 antagonists (geometric mean (95% confidence interval): 2.03 (1.9, 2.1) vs 2.63 (2.2, 3.2), respectively, p = 0.014). tumour necrosis factor-α antagonist treatment and baseline neutrophil-to-lympho-cyte ratio were independent predictors of a median low cardiovascular risk neutrophil-to-lympho-cyte ratio (< 2.15) during treatment (odds ratio (95% confidence interval): 0.53 (0.4–0.8) and 4.68 (1.0–19.1), p = 0.001 and p = 0.032, respectively). These results demonstrate a rapid and sustained reduction in biomarkers of systemic inflammation under biologic treatment. Furthermore, these data suggest class-specific effects on systemic inflammation, which may be relevant for the prevention of psoriasis co-morbidity by systemic treatment.

References

Gelfand JM. Commentary: does biologic treatment of psoriasis lower the risk of cardiovascular events and mortality? A critical question that we are only just beginning to answer. J Am Acad Dermatol 2018; 79: 69-70.

https://doi.org/10.1016/j.jaad.2018.03.046

Abuabara K, Azfar RS, Shin DB, Neimann AL, Troxel AB, Gelfand JM. Cause-specific mortality in patients with severe psoriasis: a population-based cohort study in the U.K. Br J Dermatol 2010; 163: 586-592.

https://doi.org/10.1111/j.1365-2133.2010.09941.x

Gulliver W. Long-term prognosis in patients with psoriasis. Br J Dermatol 2008; 159: 2-9.

https://doi.org/10.1111/j.1365-2133.2008.08779.x

Gulliver WP, Macdonald D, Gladney N, Alaghehbandan R, Rahman P, Adam Baker K. Long-term prognosis and comorbidities associated with psoriasis in the Newfoundland and Labrador founder population. J Cutan Med Surg 2011; 15: 37-47.

https://doi.org/10.2310/7750.2010.10013

Dantzer R. Cytokine, sickness behavior, and depression. Immunol Allergy Clin North Am 2009; 29: 247-264.

https://doi.org/10.1016/j.iac.2009.02.002

Boehncke WH. Systemic inflammation and cardiovascular comorbidity in psoriasis patients: causes and consequences. Front Immunol 2018; 9: 579.

https://doi.org/10.3389/fimmu.2018.00579

Wu JJ, Sundaram M, Cloutier M, Gauthier-Loiselle M, Guerin A, Singh R, et al. The risk of cardiovascular events in psoriasis patients treated with tumor necrosis factor-alpha inhibitors versus phototherapy: an observational cohort study. J Am Acad Dermatol 2018; 79: 60-68.

https://doi.org/10.1016/j.jaad.2018.02.050

Asahina A, Umezawa Y, Yanaba K, Nakagawa H. Serum C-reactive protein levels in Japanese patients with psoriasis and psoriatic arthritis: long-term differential effects of biologics. J Dermatol 2016; 43: 779-784.

https://doi.org/10.1111/1346-8138.13213

Garcia-Martinez P, Collado-Diaz V, Mateu-Puchades A, Villarroel-Vicente C, Rovira-Llopis S, Blas-Garcia A, et al. Differential effects of biologics on psoriasis-related vascular inflammation and risk of thrombosis. J Invest Dermatol 2020; 140: 2294-2298.e6.

https://doi.org/10.1016/j.jid.2020.02.039

Ahlehoff O, Skov L, Gislason G, Gniadecki R, Iversen L, Bryld LE, et al. Cardiovascular outcomes and systemic anti-inflammatory drugs in patients with severe psoriasis: 5-year follow-up of a Danish nationwide cohort. J Eur Acad Dermatol Venereol 2015; 29: 1128-1134.

https://doi.org/10.1111/jdv.12768

Korman NJ. Management of psoriasis as a systemic disease: what is the evidence? Br J Dermatol 2020; 182: 840-848.

https://doi.org/10.1111/bjd.18245

Bhat T, Teli S, Rijal J, Bhat H, Raza M, Khoueiry G, et al. Neutrophil to lymphocyte ratio and cardiovascular diseases: a review. Expert Rev Cardiovasc Ther 2013; 11: 55-59.

https://doi.org/10.1586/erc.12.159

Yurtdas M, Yaylali YT, Kaya Y, Ozdemir M, Ozkan I, Aladag N. Neutrophil-to-lymphocyte ratio may predict subclinical atherosclerosis in patients with psoriasis. Echocardiography 2014; 31: 1095-1104.

https://doi.org/10.1111/echo.12511

Paliogiannis P, Satta R, Deligia G, Farina G, Bassu S, Mangoni AA, et al. Associations between the neutrophil-to-lymphocyte and the platelet-to-lymphocyte ratios and the presence and severity of psoriasis: a systematic review and meta-analysis. Clin Exp Med 2019; 19: 37-45.

https://doi.org/10.1007/s10238-018-0538-x

Asahina A, Kubo N, Umezawa Y, Honda H, Yanaba K, Nakagawa H. Neutrophil-lymphocyte ratio, platelet-lymphocyte ratio and mean platelet volume in Japanese patients with psoriasis and psoriatic arthritis: response to therapy with biologics. J Dermatol 2017; 44: 1112-1121.

https://doi.org/10.1111/1346-8138.13875

Karabay E, Cerman A, Demir D, Altunay I. The effects of systemic psoriasis therapies on the C-reactive protein and the neutrophil-lymphocyte ratio. Ann Dermatol 2019; 31: 601-610.

https://doi.org/10.5021/ad.2019.31.6.601

Bland JM, Altman DG. Statistics notes: transformations, means, and confidence intervals. BMJ 1996; 312: 1079.

https://doi.org/10.1136/bmj.312.7038.1079

Kim S, Eliot M, Koestler DC, Wu WC, Kelsey KT. Association of neutrophil-to-lymphocyte ratio with mortality and cardiovascular disease in the Jackson Heart Study and modification by the duffy antigen variant. JAMA Cardiol 2018; 3: 455-462.

https://doi.org/10.1001/jamacardio.2018.1042

Zhang L, Wiles C, Martinez LR, Han G. Neutrophil-to-lymphocyte ratio decreases after treatment of psoriasis with therapeutic antibodies. J Eur Acad Dermatol Venereol 2017; 31: e491-e492.

https://doi.org/10.1111/jdv.14334

Lockshin B, Balagula Y, Merola JF. Interleukin 17, inflammation, and cardiovascular risk in patients with psoriasis. J Am Acad Dermatol 2018; 79: 345-352.

https://doi.org/10.1016/j.jaad.2018.02.040

Zaba LC, Suarez-Farinas M, Fuentes-Duculan J, Nograles KE, Guttman-Yassky E, Cardinale I, et al. Effective treatment of psoriasis with etanercept is linked to suppression of IL-17 signaling, not immediate response TNF genes. J Allergy Clin Immunol 2009; 124: 1022-10.e1-395.

https://doi.org/10.1016/j.jaci.2009.08.046

Kulig P, Musiol S, Freiberger SN, Schreiner B, Gyulveszi G, Russo G, et al. IL-12 protects from psoriasiform skin inflammation. Nat Commun 2016; 7: 13466.

https://doi.org/10.1038/ncomms13466

Elnabawi YA, Oikonomou EK, Dey AK, Mancio J, Rodante JA, Aksentijevich M, et al. Association of biologic therapy with coronary inflammation in patients with psoriasis as assessed by Perivascular Fat Attenuation Index. JAMA Cardiol 2019; 4: 885-891.

https://doi.org/10.1001/jamacardio.2019.2589

Elnabawi YA, Dey AK, Goyal A, Groenendyk JW, Chung JH, Belur AD, et al. Coronary artery plaque characteristics and treatment with biologic therapy in severe psoriasis: results from a prospective observational study. Cardiovasc Res 2019; 115: 721-728.

https://doi.org/10.1093/cvr/cvz009

Hugh J, Van Voorhees AS, Nijhawan RI, Bagel J, Lebwohl M, Blauvelt A, et al. From the Medical Board of the National Psoriasis Foundation: the risk of cardiovascular disease in individuals with psoriasis and the potential impact of current therapies. J Am Acad Dermatol 2014; 70: 168-177.

https://doi.org/10.1016/j.jaad.2013.09.020

Angel K, Provan SA, Gulseth HL, Mowinckel P, Kvien TK, Atar D. Tumor necrosis factor-alpha antagonists improve aortic stiffness in patients with inflammatory arthropathies: a controlled study. Hypertension 2010; 55: 333-338.

https://doi.org/10.1161/HYPERTENSIONAHA.109.143982

Wu JJ, Poon KY, Channual JC, Shen AY. Association between tumor necrosis factor inhibitor therapy and myocardial infarction risk in patients with psoriasis. Arch Dermatol 2012; 148: 1244-1250.

https://doi.org/10.1001/archdermatol.2012.2502

Gordon KB, Langley RG, Gottlieb AB, Papp KA, Krueger GG, Strober BE, et al. A phase III, randomized, controlled trial of the fully human IL-12/23 mAb briakinumab in moderate-to-severe psoriasis. J Invest Dermatol 2012; 132: 304-314.

https://doi.org/10.1038/jid.2011.304

Poizeau F, Nowak E, Kerbrat S, Le Nautout B, Droitcourt C, Drici MD, et al. Association between early severe cardiovascular events and the initiation of treatment with the anti-interleukin 12/23p40 antibody ustekinumab. JAMA Dermatol 2020; 156: 1208-1215.

https://doi.org/10.1001/jamadermatol.2020.2977

Rungapiromnan W, Mason KJ, Lunt M, McElhone K, Burden AD, Rutter MK, et al. Risk of major cardiovascular events in patients with psoriasis receiving biologic therapies: a prospective cohort study. J Eur Acad Dermatol Venereol 2020; 34: 769-778.

https://doi.org/10.1111/jdv.16018

Rungapiromnan W, Yiu ZZN, Warren RB, Griffiths CEM, Ashcroft DM. Impact of biologic therapies on risk of major adverse cardiovascular events in patients with psoriasis: systematic review and meta-analysis of randomized controlled trials. Br J Dermatol 2017; 176: 890-901.

https://doi.org/10.1111/bjd.14964

Lee MP, Desai RJ, Jin Y, Brill G, Ogdie A, Kim SC. Association of ustekinumab vs TNF inhibitor therapy with risk of atrial fibrillation and cardiovascular events in patients with psoriasis or psoriatic arthritis. JAMA Dermatol 2019; 155: 700-707.

https://doi.org/10.1001/jamadermatol.2019.0001

Li X, Andersen KM, Chang HY, Curtis JR, Alexander GC. Comparative risk of serious infections among real-world users of biologics for psoriasis or psoriatic arthritis. Ann Rheum Dis 2020; 79: 285-291.

https://doi.org/10.1136/annrheumdis-2019-216102

Vasan RS. Biomarkers of cardiovascular disease: molecular basis and practical considerations. Circulation 2006; 113: 2335-2362.

https://doi.org/10.1161/CIRCULATIONAHA.104.482570

Wang J, Tan GJ, Han LN, Bai YY, He M, Liu HB. Novel biomarkers for cardiovascular risk prediction. J Geriatr Cardiol 2017; 14: 135-150.

Amatore F, Villani AP, Tauber M, Viguier M, Guillot B, Psoriasis Research Group of the French Society of D. French guidelines on the use of systemic treatments for moderate-to-severe psoriasis in adults. J Eur Acad Dermatol Venereol 2019; 33: 464-483.

https://doi.org/10.1111/jdv.15340

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Published

2021-10-12

How to Cite

Hoffmann, J. H. O., Knoop, C., Enk, A. H., & Hadaschik, E. N. (2021). Detailed Long-term Dynamics of Neutrophil-to-Lymphocyte Ratio under Biologic Treatment Reveal Differential Effects of Tumour Necrosis Factor-alpha and Interleukin 12/23 Antagonists. Acta Dermato-Venereologica, 101(10), adv00568. https://doi.org/10.2340/actadv.v101.271