Dermatology: Practical and Conceptual Research Letter | Dermatol Pract Concept. 2022;12(2):e2022049 1 Tildrakizumab: Successful Response in Two Patients With Psoriatic Arthritis Dario Buononato1, Gaetano Licata1, Alessio Gambardella1, Alina De Rosa1, Giulia Calabrese1, Giuseppe Argenziano1 1 Dermatology Unit, Department of Mentals and Physical Health and Preventive medicine, University of Campania Luigi Vanvitelli, Naples, Italy. Key words: Psoriatic arthritis, psoriasis, tildrakizumab, treatment Citation: Buononato D, Licata G, Gambardella A, De Rosa A, Calabrese G, Argenziano G. Tildrakizumab: successfull response in two patients with psoriatic arthritis. Dermatol Pract Concept. 2022;12(2):e2022049. DOI: https://doi.org/10.5826/dpc.1202a49 Accepted: July 22, 2021; Published: April 2022 Copyright: ©2022 Buononato et al. This is an open-access article distributed under the terms of the Creative Commons Attribution- NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: None. Competing interests: None. Authorship: All authors have contributed significantly to this publication. Corresponding author: Dario Buononato, MD, Department of Dermatology University of Campania “Luigi Vanvitelli” via Sergio Pansini, 5, 80131 Napoli, Italy. E-mail: dario.buononato@gmail.com Introduction Psoriatic arthritis (PsA) is a chronic, immune-mediated, in- flammatory arthropathy that develops in up to 30% of pa- tients with psoriasis. Different phenotypes are recognized according to the joints involved: distal interphalangeal predominant, asymmetric oligoarticular, symmetric polyar- thritis, spondylitis and arthritis mutilans. The treatment of PsA includes different therapeutic strategies: conventional disease modifying antirheumatic drugs (DMARDs) and biologic therapies such as tumor necrosis factor (TNF) inhib- itors, interleukins-17 (IL-17) inhibitors, IL-12/23 inhibitor. However not all agents used for psoriasis are yet approved for PsA including IL-23 inhibitors: there are several cases of PsA successfully treated with IL-23 inhibitors. Case Presentation We report 2cases of patients with PsA and psoriasis (Table 1) who successfully responded to tildrakizumab, an anti-IL-23 antibody approved only for psoriasis. In the first case a 45-year-old man came to our unit with a 10 years history of PsA and psoriasis. The patient presented several episodes of dactylitis with radiologically documented damage to the distal interphalangeal joints. He had been treated with methotrexate (20 mg/week) for 9 months, sus- pended for a significant increase in transaminases (ALT 110 U/L, AST 121 U/L). We started treatment with secukinumab (300 mg sc monthly) from October 2018 to November 2019 with a partial improvement of PsA and skin disease, but the patient developed upper respiratory tract infection and the drug was stopped. Thus, the patient received tildrakizumab at the same dosage regimen as in psoriasis (100 mg sc every 12 weeks) with improvement in both diseases. In the second case a 56-year-old woman came to our unit with a 15 years history of PsA and psoriasis. The patient suffered from peripheral asymmetric oligoarticular arthritis associated with bilateral uveitis, treated periodically with methotrexate (15 mg/week) interrupted because of several relapses. From October 2019 to September 2020, she began therapy with adalimumab (40 mg sc every 2 weeks), then stopped for the appearance of itching and skin rash. Given 2 Research Letter | Dermatol Pract Concept. 2022;12(2):e2022049 the impossibility of carrying out therapy with IL-17 inhib- itors due to a suspected concomitant ulcerative colitis, we started therapy with tildrakizumab from December 2020, getting a control of PsA. Conclusions IL-23/IL-17 cytokines are important players in the patho- genesis of PsA. In particular, IL-23 stabilizes the Th17 phe- notype, supporting secretion of IL-17 which mediate the epidermal hyperplasia and keratinocyte differentiation. Moreover IL-23 activates the production of LTB4, exacer- bating the synovial inflammation, and induces osteoclast dif- ferentiation with bone resorption result [1]. We have demonstrated that tildrakizumab is a valid therapeutic option in patients suffering from PsA, as it acts inhibiting the IL-23/IL-17 axis, the signaling pathway pri- marily dysregulated in this condition. It has never been de- scribed cases of patients with PsA and concomitant psoriasis with favorable response to tildrakizumab. Recent studies have been published on the approval of guselkumab in PsA [2]: considering that IL-23 is the same target, also tildraki- zumab could be a useful therapeutic option for this affection. Further studies are required to evaluate the efficacy and safety of tildrakizumab in larger cohorts of patients to con- sider this IL-23 inhibitor as a new promising treatment op- tion for PsA. References 1. Nguyen CT, Bloch Y, Składanowska K, Savvides SN, Adam- opoulos IE.. Pathophysiology and inhibition of IL-23 signal- ing in psoriatic arthritis: A molecular insight. Clin Immunol. 2019;206:15-22. DOI: 10.1016/j.clim.2018.09.002. PMID: 30196070. PMCID: PMC6401348. 2. Boehncke WH, Brembilla NC, Nissen MJ. Guselkumab: the First Selective IL-23 Inhibitor for Active Psoriatic Arthritis in Adults. Expert Rev Clin Immunol. 2021;17(1):5-13. DOI 10.1080/1744666X.2020.1857733. PMID: 33251833. Table 1. Patients clinical details with tildrakizumab treatment for psoriatic arthritis Patient 1 Patient 2 Gender Male Female Age, years 45 56 Psoriatic arthritis phenotype Distal interphalangeal joints Asymmetric oligoarticular joints Systemic involvement Psoriasis Psoriasis Uveitis Treatment before tildrakizumab Methotrexate Secukinumab Methotrexate Adalimumab