Adverse Events and Immune Response in Psoriasis Patients Receiving Interleukin-17 Inhibitors
DOI:
https://doi.org/10.2340/actadv.v105.43685Keywords:
Adalimumab, Candidiasis, Immunity, Inflammatory Bowel Diseases, Interleukin-17, S100 ProteinsAbstract
Interleukin-17 inhibitors are effective in psoriasis; however, they are associated with an increased risk of infections, particularly oral candidiasis, and new-onset/flares of inflammatory bowel disease. This study aimed to identify predictive markers for these adverse events and to describe the functional immune response in patients treated with interleukin-17 inhibitors using a whole-blood stimulation system (TruCulture®). Patients with psoriasis initiating an interleukin-17 inhibitor (n = 36) or adalimumab (n = 24) were enrolled. Patients attended visits at baseline, week 12, and week 52, during which skin and mucosal swabs, and faecal and blood samples were collected. Baseline oral Candida albicans colonization with no clinical symptoms was associated with an increased risk of oral candidiasis during the first year of interleukin-17 inhibitor therapy, with no cases of oral candidiasis observed in the adalimumab group. Gut inflammation, measured by faecal calprotectin, remained stable in both the adalimumab and interleukin-17 inhibitor group. Colonization with Staphylococcus aureus did not change during treatment. It was found that interleukin-17 inhibitors induced an anti-inflammatory state and potentially more active toll-like receptor 3-mediated antiviral responses compared with adalimumab. In conclusion, screening for oral Candida albicans colonization prior to initiation of interleukin-17 inhibitor therapy may be a useful strategy for risk stratification and early intervention.
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Sbidian E, Chaimani A, Guelimi R, Garcia-Doval I, Hua C, Hughes C, et al. Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis. Cochrane Database Syst Rev 2023; 7: 6689. DOI: https://doi.org/10.1002/14651858.CD011535.pub6
Reich K, Warren RB, Lebwohl M, Gooderham M, Strober B, Langley RG, et al. Bimekizumab versus secukinumab in plaque psoriasis. N Engl J Med 2021; 385: 142–152. DOI: https://doi.org/10.1056/NEJMoa2102383
Cho JS, Pietras EM, Garcia NC, Ramos RI, Farzam DM, Monroe HR, et al. IL-17 is essential for host defense against cutaneous Staphylococcus aureus infection in mice. J Clin Invest 2010; 120: 1762–1773. DOI: https://doi.org/10.1172/JCI40891
Mills KHG. IL-17 and IL-17-producing cells in protection versus pathology. Nat Rev Immunol 2023; 23: 38–54. DOI: https://doi.org/10.1038/s41577-022-00746-9
Puel A, Cypowyj S, Bustamante J, Wright JF, Liu L, Lim HK, et al. Chronic mucocutaneous candidiasis in humans with inborn errors of interleukin-17 immunity*. Science 2011; 332: 65–68. DOI: https://doi.org/10.1126/science.1200439
Saunte DM, Mrowietz U, Puig L, Zachariae C. Candida infections in patients with psoriasis and psoriatic arthritis treated with interleukin-17 inhibitors and their practical management. Br J Dermatol 2017; 177: 47–62. DOI: https://doi.org/10.1111/bjd.15015
D’Enfert C, Kaune AK, Alaban LR, Chakraborty S, Cole N, Delavy M, et al. The impact of the fungus-host-microbiota interplay upon Candida albicans infections: current knowledge and new perspectives. FEMS Microbiol Rev 2021; 45: 14. DOI: https://doi.org/10.1093/femsre/fuaa060
Sparber F, Leibundgut-Landmann S. Interleukin-17 in antifungal immunity. Pathogens 2019; 8: 54. DOI: https://doi.org/10.3390/pathogens8020054
Ferrante M, Panaccione R, Baert F, Bossuyt P, Colombel JF, Danese S, et al. Risankizumab as maintenance therapy for moderately to severely active Crohn’s disease: results from the multicentre, randomised, double-blind, placebo-controlled, withdrawal phase 3 FORTIFY maintenance trial. Lancet 2022; 399: 2031–2046. DOI: https://doi.org/10.1016/S0140-6736(22)00466-4
Hueber W, Sands BE, Lewitzky S, Vandemeulebroecke M, Reinisch W, Higgins PDR, et al. Secukinumab, a human anti-IL-17A monoclonal antibody, for moderate to severe Crohn’s disease: unexpected results of a randomised, double-blind placebo-controlled trial. Gut 2012; 61: 1693–1700. DOI: https://doi.org/10.1136/gutjnl-2011-301668
Targan SR, Feagan B, Vermeire S, Panaccione R, Melmed GY, Landers C, et al. A randomized, double-blind, placebo-controlled phase 2 study of brodalumab in patients with moderate-to-severe Crohn’s disease. Am J Gastroenterol 2016; 111: 1599–1607. DOI: https://doi.org/10.1038/ajg.2016.298
Loft ND, Vaengebjerg S, Halling AS, Skov L, Egeberg A. Adverse events with IL-17 and IL-23 inhibitors for psoriasis and psoriatic arthritis: a systematic review and meta-analysis of phase III studies. J Eur Acad Dermatol Venereol 2020; 34: 1151–1160. DOI: https://doi.org/10.1111/jdv.16073
Whibley N, Gaffen SL. Gut-busters: IL-17 ain’t afraid of no IL-23. Immunity 2015; 43: 620. DOI: https://doi.org/10.1016/j.immuni.2015.10.001
Bruno M, Davidson L, Koenen HJPM, van den Reek JMPA, van Cranenbroek B, de Jong EMGJ, et al. Immunological effects of anti‒IL-17/12/23 therapy in patients with psoriasis complicated by candida infections. J Invest Dermatol 2022; 142: 2929–2939.e8. DOI: https://doi.org/10.1016/j.jid.2022.05.1083
Smolen JS, Mease P, Tahir H, Schulze-Koops H, De La Torre I, Li L, et al. Multicentre, randomised, open-label, parallel-group study evaluating the efficacy and safety of ixekizumab versus adalimumab in patients with psoriatic arthritis naive to biological disease-modifying antirheumatic drug: final results by week 52. Ann Rheum Dis 2020; 79: 1310–1319. DOI: https://doi.org/10.1136/annrheumdis-2020-217372
Todberg T, Loft N, Møller DL, Ostrowski SR, Nielsen SD, Skov L. Impact of methotrexate and adalimumab on immune function of patients with psoriasis. Dermatol Ther 2022; 35: e15284. DOI: https://doi.org/10.1111/dth.15284
Tracey D, Klareskog L, Sasso EH, Salfeld JG, Tak PP. Tumor necrosis factor antagonist mechanisms of action: a comprehensive review. Pharmacol Ther 2008; 117: 244–279. DOI: https://doi.org/10.1016/j.pharmthera.2007.10.001
von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet 2007; 370: 1453–1457. DOI: https://doi.org/10.1016/S0140-6736(07)61602-X
Østgård RD, Deleuran BW, Dam MY, Hansen IT, Jurik AG, Glerup H. Faecal calprotectin detects subclinical bowel inflammation and may predict treatment response in spondyloarthritis. Scand J Rheumatol 2018; 47: 48–55. DOI: https://doi.org/10.1080/03009742.2017.1299216
R Core Team (2022). R: A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing. https://www.R-project.org/
Elsner K, Holstein J, Hilke FJ, Blumenstock G, Walker B, Schmidt S, et al. Prevalence of Candida species in psoriasis. Mycoses 2022; 65: 247–254. DOI: https://doi.org/10.1111/myc.13399
Picciani BLS, Michalski-Santos B, Carneiro S, Sampaio AL, Avelleira JCR, Azulay DR, et al. Oral candidiasis in patients with psoriasis: correlation of oral examination and cytopathological evaluation with psoriasis disease severity and treatment. J Am Acad Dermatol 2013; 68: 986–991. DOI: https://doi.org/10.1016/j.jaad.2012.11.033
Gordon KB, Langley RG, Warren RB, Okubo Y, Stein Gold L, Merola JF, et al. Bimekizumab safety in patients with moderate to severe plaque psoriasis: pooled results from phase 2 and phase 3 randomized clinical trials. JAMA Dermatol 2022; 158: 735–744. DOI: https://doi.org/10.1001/jamadermatol.2022.1185
Lemberg C, de San Vicente KM, Fróis-Martins R, Altmeier S, Tran VDT, Mertens S, et al. Candida albicans commensalism in the oral mucosa is favoured by limited virulence and metabolic adaptation. PLoS Pathog 2022; 18: e1010012. DOI: https://doi.org/10.1371/journal.ppat.1010012
Brizzi D, Rocco EV, Veronica E, Rocco A, Babino G, Buononato D, et al. evaluation of the role of faecal calprotectin in the management of psoriatic patients under treatment with biologic drugs. Biomedicines 2022; 10: 2968. DOI: https://doi.org/10.3390/biomedicines10112968
Fu Y, Lee CH, Chi CC. Association of psoriasis with inflammatory bowel disease: a systematic review and meta-analysis. JAMA Dermatol 2018; 154: 1417–1423. DOI: https://doi.org/10.1001/jamadermatol.2018.3631
Burisch J, Eigner W, Schreiber S, Aletaha D, Weninger W, Trauner M, et al. Risk for development of inflammatory bowel disease under inhibition of interleukin 17: a systematic review and meta-analysis. PLoS One 2020; 15: e0233781. DOI: https://doi.org/10.1371/journal.pone.0233781
Duffy D, Rouilly V, Libri V, Hasan M, Beitz B, David M, et al. Functional analysis via standardized whole-blood stimulation systems defines the boundaries of a healthy immune response to complex stimuli. Immunity 2014; 40: 436–450. DOI: https://doi.org/10.1016/j.immuni.2014.03.002
Blauvelt A. IL-6 differs from TNF-α: unpredicted clinical effects caused by IL-6 blockade in psoriasis. J Invest Dermatol 2017; 137: 541–542. DOI: https://doi.org/10.1016/j.jid.2016.11.022
Grän F, Kerstan A, Serfling E, Goebeler M, Muhammad K. Current developments in the immunology of psoriasis. Yale J Biol Med 2020; 93: 97.
Perales-Linares R, Navas-Martin S. Toll-like receptor 3 in viral pathogenesis: friend or foe? Immunology 2013; 140: 153–167. DOI: https://doi.org/10.1111/imm.12143
Kridin K, Zirpel H, Mruwat N, Ludwig RJ, Thaci D. Evaluating the risk of infections under interleukin 23 and interleukin 17 inhibitors relative to tumour necrosis factor inhibitors: a population-based study. J Eur Acad Dermatol Venereol 2023; 37: 2319–2326. DOI: https://doi.org/10.1111/jdv.19328
Glintborg B, Di Giuseppe D, Wallman JK, Provan SA, Nordström D, Hokkanen AM, et al. Is the risk of infection higher during treatment with secukinumab than with TNF inhibitors? An observational study from the Nordic countries. Rheumatology 2023; 62: 647–658. DOI: https://doi.org/10.1093/rheumatology/keac358
Rezahosseini O, Liljendahl MS, Loft N, Møller DL, Harboe ZB, Rasmussen MK, et al. Incidence, risk factors, and consequences of human alphaherpesvirus infections in patients with psoriasis who initiate methotrexate or biologic agents. J Infect Dis 2022; 226: 1510–1518. DOI: https://doi.org/10.1093/infdis/jiac367
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Copyright (c) 2025 Christopher Willy Schwarz, Charlotte Näslund-Koch, Claus Zachariae, Jakob Benedict Seidelin, Susanne Dam Nielsen, Sisse Rye Ostrowski, Karen Marie Thyssen Astvad, Inger Brock, Lars Iversen, Mads Kirchheiner Rasmussen, Nikolai Loft, Lone Skov
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