THU0149 JAK KINASE INHIBITORS AND VARICELLA ZOSTER VIRUS INFECTION IN PATIENTS WITH RHEUMATOID ARTHRITIS. SYSTEMATIC REVIEW OF THE LITERATURE.
Authors: C. O. Sánchez Gonzalez, J. C. Nieto
Journal: Annals of the Rheumatic Diseases (2020)

Background: Objectives: Objetive: To assess the incidence of Herpes Zoster (HZ) infection in patients with Rheumatoid Arthritis (RA) treated with JAKi. Methods: Method: We conducted a systematic literature review searching in Medline, Embase and Cochrane. The final date was set on December 31, 2019, and only articles in English were included. See the following terms: rheumatoid arthritis, herpes zoster and the different JAK kinase inhibitors studied: tofacitinib, baricitinib, upadacitinib, filgotinib, peficitinib and decernotinib. Conference abstract, case series and clinical practice records were excluded. Only phase II and phase III clinical trials were included, as well as extension studies, with the following criteria: - Patients diagnosed with RA according to the American College of Rheumatology Criteria and /or EULAR criteria. - Drugs evaluated: tofacitinib, baricitinib, upadacitinib, filgotinib, peficitinib or decernotinib, all of them compared with placebo. - Safety data on HZ infection. The search included a total of 2521 publications of which 504 were duplicated, leaving 2017. After screening by title and abstract 1874 studies that did not meet the criteria were eliminated and there were 143 fully reviewed. At the end 42 papers were included in the review. The main objective of our study was the number of HZ infections depending on the doses of the drug administered, as well as with placebo. Data collected from each study was: Author and year of publication of the study, study design and population included, number of patients treated, treatment administered and percentage of patients treated for HZ in each treatment arm. Results: Results: In clinical trials of these drugs, a greater number of opportunistic infections due to varicella zoster virus have been identified compared to placebo, which leads to the appearance of HZ. The role of different JAKs in the immune response may suggest differences in safety profiles between these drugs, which could have clinical implications. Therefore, we analyze the results separately for each JAKi. Tofacitinib Of the 14 selected works, 4 are phase II, 8 phase III and 2 extension studies. We observe that the incidence of HZ ranges between 1% and 11%, the latter being the case of the Wollenhaupt extension study with a data collection period of nine and a half years. It is remarkable that in some of the studies included in this review there was no case of HZ and in others this information was not even collected. Baricitinib Two phase II studies, 6 phase III studies and one extension study were analyzed, with an incidence of HZ between 1% and 9%, data similar to those obtained with tofacitinib. Upadacitinib. An incidence of HZ between 1% and 4% was observed according to the 6 clinical trials (two phase II studies and four phase III studies) published as clinical product development. Filgotinib Data similar to upadacitinib, with frequencies between 1% and 4% of HZ according to the studies (three phase II studies and one phase III study). Peficitinib The incidence of HZ ranged between 4% and 7.5% (three phase II studies, two phase III studies, and one extension study). Decernotinib There are only published three phase II trials, of short duration and with only four cases collected from HZ. Conclusion: Conclusions: Opportunistic HZ infection have been reported between 1% and 11% in JAKi clinical trials. The results of the included studies seem to suggest that selective JAK1 inhibitors (Upadacitinib and Filgotinib) develop HZ as a treatment complication less frequently than other JAKi, but more studies are needed to support this conclusion. Disclosure of Interests: Carmen Olga Sánchez Gonzalez: None declared, Juan Carlos Nieto Speakers bureau: Pfizer, Abbvie, MSD, Novartis, Janssen, Lilly, Nordic Pharma, BMS, Gebro, FAES Farma, Roche, Sanofi