Risk of candidiasis associated with interleukin-17 inhibitors: A real-world observational study of multiple independent sources

被引:66
作者
Davidson, Linda [1 ,2 ]
van den Reek, Juul M. P. A. [3 ]
Bruno, Mariolina [1 ,2 ]
van Hunsel, Florence [4 ]
Herings, Ron M. C. [5 ,6 ]
Matzaraki, Vasiliki [1 ,2 ,7 ]
Boahen, Collins K. [1 ,2 ]
Kumar, Vinod [1 ,2 ,7 ]
Groenewoud, Hans M. M. [8 ]
van de Veerdonk, Frank L. [1 ,2 ]
Netea, Mihai G. [1 ,2 ,9 ]
de Jong, Elke M. G. J. [3 ]
Kullberg, Bart Jan [1 ,2 ]
机构
[1] Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, Nijmegen, Netherlands
[2] Radboud Univ Nijmegen, Radboudumc Ctr Infect Dis RCI, Med Ctr, Nijmegen, Netherlands
[3] Radboud Univ Nijmegen, Med Ctr, Dept Dermatol, Nijmegen, Netherlands
[4] Netherlands Pharmacovigilance Ctr Lareb, Shertogenbosch, Netherlands
[5] PHARMO Inst Drug Outcomes Res, Utrecht, Netherlands
[6] Amsterdam UMC Vrije Univ, Dept Epidemiol & Data Sci, Amsterdam Cardiovasc Sci, Amsterdam Publ Hlth, Amsterdam, Netherlands
[7] Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands
[8] Radboud Univ Nijmegen, Med Ctr, Dept Hlth Evidence, Nijmegen, Netherlands
[9] Univ Bonn, Life & Med Sci Inst LIMES, Dept Immunol & Metab, Bonn, Germany
来源
LANCET REGIONAL HEALTH-EUROPE | 2022年 / 13卷
关键词
Candidiasis; IL-17; inhibitors; IL-12/23; Drug safety; Pharmacovigilance; ustekinumab; secukinumab; ixekizumab; PLAQUE PSORIASIS; DRUG SURVIVAL; DOUBLE-BLIND; SECUKINUMAB; ALBICANS; USTEKINUMAB; CHEMOKINES; MODERATE; PHASE-3; MULTICENTER;
D O I
10.1016/j.lanepe.2021.100266
中图分类号
R19 [保健组织与事业(卫生事业管理)];
学科分类号
摘要
Background Biologics directed against the T-helper (Th)-17 pathway have been approved for several inflammatory diseases. Interleukin (IL)-17 is involved in anti-Candida host defense, and clinical trials suggested increased candidiasis incidence during IL-17 inhibitor therapy. We describe the worldwide epidemiology of candidiasis during Th17 inhibitor therapy, and immunological mechanisms involved in candidiasis susceptibility. Methods A comprehensive analysis of multiple independent sources reporting Candida adverse events during biologics inhibiting the Th17 pathway was performed. Association between Th17 inhibitors and candidiasis was assessed using safety reports of (1) WHO and (2) EMA, (3) a population-based prescriptions registry, and (4) a psoriasis cohort. In a cohort of psoriasis patients experiencing candidiasis during Th17 inhibitors, Candida killing by immune cells and serum inflammatory proteome were analyzed. Findings A strong association between IL-17 inhibitors and candidiasis (ROR 10.20) was found in the WHO database, particularly for cutaneous (ROR 12.28), oropharyngeal (ROR 19.18), and esophageal candidiasis (ROR 21.20). Risk was higher relative to TNF-alpha inhibitors (4-10-fold, depending on candidiasis type), confirmed by EMA reports (16-33-fold), prescriptions registry (2-42-fold), and a psoriasis cohort (3-25-fold). After start of IL-17 inhibitors, patients' risk of candidiasis requiring antifungals increased 2-16 fold. In the psoriasis cohort, 58% of IL-17 treatment episodes were associated with candidiasis. In Th17 inhibitor recipients, proteins involved in anti-Candida immunity and Candida killing by mononuclear leukocytes were impaired. Interpretation IL-17 inhibitors are associated with an increased risk of oropharyngeal, esophageal, and cutaneous candidiasis, posing a significant disease burden for IL-17 inhibitor recipients. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.
引用
收藏
页数:13
相关论文
共 42 条
  • [21] 2-C
  • [22] An integrated model of the recognition of Candida albicans by the innate immune system
    Netea, Mihai G.
    Brown, Gordon D.
    Kullberg, Bart Jan
    Gow, Neil A. R.
    [J]. NATURE REVIEWS MICROBIOLOGY, 2008, 6 (01) : 67 - 78
  • [23] Immune defence against Candida fungal infections
    Netea, Mihai G.
    Joosten, Leo A. B.
    van der Meer, Jos W. M.
    Kullberg, Bart-Jan
    van de Veerdonk, Frank L.
    [J]. NATURE REVIEWS IMMUNOLOGY, 2015, 15 (10) : 630 - 642
  • [24] Shrinkage observed-to-expected ratios for robust and transparent large-scale pattern discovery
    Noren, G. Niklas
    Hopstadius, Johan
    Bate, Andrew
    [J]. STATISTICAL METHODS IN MEDICAL RESEARCH, 2013, 22 (01) : 57 - 69
  • [25] Chronic mucocutaneous candidiasis disease associated with inborn errors of IL-17 immunity
    Okada, Satoshi
    Puel, Anne
    Casanova, Jean-Laurent
    Kobayashi, Masao
    [J]. CLINICAL & TRANSLATIONAL IMMUNOLOGY, 2016, 5
  • [26] Olink, VAL DOC INFL PAN 201
  • [27] Chronic Mucocutaneous Candidiasis in Humans with Inborn Errors of Interleukin-17 Immunity
    Puel, Anne
    Cypowyj, Sophie
    Bustamante, Jacinta
    Wright, Jill F.
    Liu, Luyan
    Lim, Hye Kyung
    Migaud, Melanie
    Israel, Laura
    Chrabieh, Maya
    Audry, Magali
    Gumbleton, Matthew
    Toulon, Antoine
    Bodemer, Christine
    El-Baghdadi, Jamila
    Whitters, Matthew
    Paradis, Theresa
    Brooks, Jonathan
    Collins, Mary
    Wolfman, Neil M.
    Al-Muhsen, Saleh
    Galicchio, Miguel
    Abel, Laurent
    Picard, Capucine
    Casanova, Jean-Laurent
    [J]. SCIENCE, 2011, 332 (6025) : 65 - 68
  • [28] Reich K, 2021, LANCET, V397, P487, DOI 10.1016/S0140-6736(21)00125-2
  • [29] The reporting odds ratio and its advantages over the proportional reporting ratio
    Rothman, KJ
    Lanes, S
    Sacks, ST
    [J]. PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, 2004, 13 (08) : 519 - 523
  • [30] Candida infections in patients with psoriasis and psoriatic arthritis treated with interleukin-17 inhibitors and their practical management
    Saunte, D. M.
    Mrowietz, U.
    Puig, L.
    Zachariae, C.
    [J]. BRITISH JOURNAL OF DERMATOLOGY, 2017, 177 (01) : 47 - 62