CLINICAL REPORT
829 ActaDV ActaDV Advances in dermatology and venereology Acta Dermato-Venereologica
Safety Profile of Secukinumab in Treatment of Patients with Psoriasis and Concurrent Hepatitis B or C: A Multicentric Prospective Cohort Study
Hsien-Yi CHIU 1 – 4, Rosaline Chung-yee HUI 5 – 7, Yu-Huei HUANG 5 – 7, Ruey-Yun HUANG 1, Kai-Lung CHEN 1, 3, 4, Ya-Chu TSAI 8, Po-Ju LAI 9, 10, Ting-Shun WANG 3, 4, 9, 10 and Tsen-Fang TSAI 3, 4 Departments of Dermatology: 1 National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, 3 National Taiwan University Hospital, 4 College of Medicine, National Taiwan University, Taipei, 5 Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, 7 Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, 8 Far Eastern Memorial Hospital, New Taipei, 9 Chung Shan Medical University Hospital, Taichung, Taiwan and 10 Chung Shan Medical University, Taichung, 2 Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, and 6 School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
Safety data for secukinumab in patients with psoriasis and viral hepatitis are lacking. The aim of this study is to investigate the risk of reactivation of hepatitis B virus( HBV)/ hepatitis C virus( HCV) in patients with psoriasis who are receiving secukinumab therapy. This multicentre study screened 284 patients with psoriasis with available HBV and HCV serological data and 63 patients with concurrent HBV / HCV infection were enrolled. In the absence of antiviral prophylaxis, 7 of 46( 15.2 %) patients with HBV exhibited HBV reactivation during secukinumab therapy. The risk of reactivation was significantly higher in HBsAg-positive patients, compared with HBsAg-negative / HBcAb-positive patients( 24.0 % vs. 4.17 %, p = 0.047). One of 14( 7.1 %) HCV patients showed enhanced replication of HCV with hepatitis. No virus reactivation occurred in patients receiving antiviral prophylaxis. HBsAg-positive and HBsAg-negative / HBcAb-positive psoriasis patients can develop virus reactivation during secukinumab therapy, thus necessitating close monitoring of viral load and considering an antiviral prophylaxis for all HBsAg-positive patients with psoriasis.
Key words: psoriasis; secukinumab; hepatitis B; hepatitis C; interleukin-17A inhibitor; biologics.
Accepted Jun 5, 2018; Epub ahead of print Jun 8, 2018 Acta Derm Venereol 2018; 98: 829 – 834.
Corr: Tsen-Fang Tsai, Department of Dermatology, National Taiwan University Hospital, No. 7 Chung San South Road, Taipei, Taiwan. E-mail: tftsai @ yahoo. com
In the past decade, the emergence of biologic therapies, including anti-tumour necrosis factor( anti-TNF-α), anti-interleukin( anti-IL) 12 / 23 p40 monoclonal antibody, and the recently approved anti-IL-17 / IL-17R antibody, has substantially improved the treatment outcome of patients with psoriasis( 1). However, safety concerns over the use of biologics still exist, especially in view of opportunistic infections, such as those caused by mycobacterial, bacterial, viral and fungal agents( 2). Moreover, biologic agents alter the competence of the host immune-surveillance system to combat hepatitis virus infections, which may increase virus reactivation and replication, resulting in injury to the liver( 3, 4). Recent years have witnessed an
SIGNIFICANCE
This study showed that biologic agents alter the competence of the host immune-surveillance system to combat hepatitis virus infections and hepatitis B virus( HBV) or hepatitis C virus( HCV). Reactivation can occur in patients with psoriasis with concurrent HBV or HCV treated with secukinumab, an anti-interleukin 17 agent. The risk of virus reactivation varied in patients with psoriasis with different virological profiles. It is advisable to monitor the viral load / serum transaminase level and consider antiviral prophylaxis for all hepatitis B surface antigen-positive patients with psoriasis who are being treated with secukinumab.
increase in the number of cases of reactivation of hepatitis B( HBV) or hepatitis C( HCV) virus in patients with psoriasis who are receiving biologics( 3, 5, 6).
Secukinumab, a monoclonal antibody that selectively binds and neutralizes IL-17A, has demonstrated high efficacy in treating moderate-to-severe plaque psoriasis( 7). However, IL-17, a major effector cytokine of T-helper 17( Th17), has been shown to mediate host defence mechanisms in response to various infective agents( 8). Emerging research has also shown that Th17 response is involved in various viral infections( 9 – 11). Studies suggest that IL-17 plays a role in eliciting innate defence at mucosal sites and inducing infection-associated immunopathology during viral infections( 12). Moreover, Th17 response is involved in the pathogenesis of viral hepatitis. The number of intrahepatic IL-17 and circulating IL-17-producing peripheral blood mononuclear cells was found to be significantly increased in patients with HBV and HCV infection( 4). Available data also suggest that IL-17 plays an important role in suppressing HBV activity( 4), and that Th17 cells drive the immune-mediated pathology of HBV and HCV( 4). However, safety data for secukinumab in patients with psoriasis and viral hepatitis are lacking because these patients are always excluded from pivotal trials. Therefore, we conducted a multicentre study to assess the risk of virus reactivation in patients with psoriasis with concurrent HBV or HCV infection during secukinumab therapy and the usefulness of antiviral prophylaxis in real-life practice.
This is an open access article under the CC BY-NC license. www. medicaljournals. se / acta Journal Compilation © 2018 Acta Dermato-Venereologica. doi: 10.2340 / 00015555-2989 Acta Derm Venereol 2018; 98: 829 – 834