AB0362 HERPES ZOSTER IN BARICITINIB-TREATED JAPANESE PATIENTS WITH RHEUMATOID ARTHRITIS USING REAL-WORLD CLINICAL DATA
Authors: E. Torikai, Y. Hirano, D. Suzuki, Y. Kanayama
Journal: Annals of the Rheumatic Diseases (2020)

Background: Similar to biologic disease-modifying anti-rheumatic drugs, the association between Janus kinase (JAK) inhibitors and infection is particularly interesting. The incidence of herpes zoster (HZ) among patients treated with JAK inhibitors is twofold to threefold higher in several regions of Asia (e.g., Japan and Korea) as compared with that observed in North America and Western Europe [1]. Objectives: To evaluate the characteristics of patients who developed HZ during baricitinib treatment using real-world, multicenter, clinical data for Japanese population. Methods: The study enrolled 97 patients with rheumatoid arthritis (RA) who were treated with baricitinib therapy (68 biologic-naïve patients and 29 biologic-experienced patients) were enrolled in the study (observation period: 2–27 months). The severity of HZ infection was determined based on the extent of the rash and the presence or absence of organ damage. We evaluated the characteristics and clinical courses of patients who developed HZ. Results: Eight patients with HZ. The incidence ratio (IR) was 8.2 per patient-year. Patient data are described in Table 1 and Table 2. The IR was a little higher than that reported in clinical trials [2], which could be attributed to the high average age (i.e., 67.3 years) of the patients in this study. It was reported that adverse events occurred more frequently in elderly patients aged ≥65 years compared with younger patients [3]. The period from baricitinib administration to the onset of HZ varied between 2 months and 16 months. It is suggested that HZ may develop at any time during baricitinib therapy. There were no distinctive patient characteristics, except for age, at the time of initial baricitinib administration between patients who developed HZ and those who did not. Table 2. Response rates of non-medical Switch from Cellcept to Myfortic Case- No. Age (years) Time (years) from RA onset Gender Female:F Male: M) BMI Bari dose (mg/d) PSL(mg/d) MTX (mg/w) HZ history Number of prior biologics 1 74 1.5 F 25.6 4 0 12 No 2 2 61 33 F 19.2 2 0 6 No 1 3 61 11.1 F 23.6 4 0 10 Yes 0 4 73 0.5 M 23.3 4 0 8 Yes 0 5 74 21.9 F 20.9 2 0 0 No 0 6 78 1.2 F 19.8 4 0 6 No 0 7 48 23.2 F 24.1 4 4 8 No 0 8 79 5.0 F 22.4 2 2.5 4 No 0 Table 1. Fatigue in NPSLE and non-NPSLE patients (N = 222) Case No. HZ incidence period after baricitinib administration (months) Priod of baricitinib withdrawal (weeks) Severity (Mild; Mil Moderate: Mod) 1 16 4 Mod 2 2 4 Mod 3 13 1 Mil 4 3 1 Mil 5 8 6 Mod 6 3 4 Mil ~ Mod 7 3 3 Mod 8 20 Discontinuation due to pateient’s choice Mod None of the patients had severe symptoms, and none of them experienced organ damage. All patients were cured with anti-viral agents. It should be noted that patients who had a history of HZ had milder symptoms than those who had no history of HZ. We noted an interesting finding in one patient (case 2). The half-life of baricitinib in the blood was very short (about 6 hours), and it is reported that the drug is almost fully excreted from the body 24 hours after its administration [4]. However, this patient developed an incidence of HZ at 17 days after the withdrawal of baricitinib for surgery management. Cells may take longer time to regain their original immune status even after excretion of the drug, especially, during intense stress such as in cases of surgical invasion. Conclusion: The HZ risk in Japanese patients with RA treated with baricitinib in real-world practice was high, especially in elderly patients. It is notable that HZ events were nonserious and that patients could restart baricitinib treatment after healing with antiviral therapy, for the most part. References: [1]Taylor PC et al. N Engl J Med. 2017;376:652-62 [2]Harigai M et al. Mod Reumatol. 2019;20:1-8. [3]Fleischmann R et al. RMD open. 2017;3:e000546. [4]Shi JG et al. J Clin Pharmacol. 2014;54:1354-61 Disclosure of Interests: Eiji Torikai: None declared, Yuji Hirano Speakers bureau: Tanabe-Mitsubishi, Pfizer, Eisai, Abbie, Chugai, Bristol-Meyers, Jansen, Astellas, UCB, Eli-Lilly, Asahikasei, Daiichi-Sankyo, Amgen, Daisuke Suzuki: None declared, Yasuhide Kanayama: None declared