AB1458 JAK INHIBITORS AND VENOUS THROMBOEMBOLISM EVENTS - REASSURING DATA FROM A LARGE SINGLE CENTRE RETROSPECTIVE STUDY

Abstract

BackgroundIn March 2021, the European Medicines Agency (EMA) sent out a Medicine Alert related Xeljanz (tofacitinib): The Initial clinical trial results suggested an increased risk of major adverse cardiovascular events and malignancies with use of tofacitinib relative to TNF-alpha inhibitors.In light of these safety alerts, March 2021, the Rheumatology department at Portsmouth Hospitals University NHS Trust updated the Biologics Screening documents to include a cardiovascular and venous thromboembolism (VTE) risk assessment.We conducted a retrospective observational study to document the incidence of VTE in patients on Janus kinase (JAK) inhibitors admitted to our Venous thromboembolism Service from 14th April 2018 to 30th November 2021 (43 months).This includes patients who were suspected of having both deep vein thrombosis (DVT) and/or Pulomonary Thromboembolisim (PE). We were particularly interested to assess whether any patients with VTE events had been receiving JAK inhibitors given the potential association of JAK inhibitor usage and VTE.ObjectivesTo establish whether patients exposed to JAK inhibitors had any increased incidence of VTE. This was done through a retrospective analysis for all patients presenting to Portsmouth Hospitals University NHS Trust.MethodsWe utilised the International Classification of Diseases (ICD10) diagnosis code of I82 (182.0, 182.1,182.2,128.3,182.8,1782.9). This includes; Budd Chiari syndrome, thrombophlebitis migrans, embolism and thrombosis of vena cava, embolism and thrombosis renal vein, embolism and thrombosis of other specified view and embolism and thrombosis unspecified vein. From this data set, we reviewed how many case of VTE were noted in patients on JAK inhibitors. The Data was confined to patients who underwent diagnostic tests for VTE at Portsmouth Hospials University NHS Trust.ResultsA total of 417 patients had been admitted to the VTE Service for diagnostic assessment between 14th April 2018 to 30th November 2021.A total of 261 patients had been on a JAK inhibitor during the period of observation. This included patients on Tofacitinib, Baricitinib, Filgotinib and Upadacitinib. This was for treatment in Rheumatoid Arthritis and Psoriatic Arthritis where liscenced indications were appropriate.None of these had a VTE event. The age range of the patients on active treatment was 18 to 86 years old with the average of 60.7 years. The majority of patients were female (72.7%) with male patients comprising the remainder (27.3%).8 patients under the care of the Rheumatology service were identified as having VTE events.ConclusionFrom a total of 261 patients on JAK inhibitors during a 43 month period; 0 patients had a confirmed VTE event.After March 2021, the Rheumatology department soutght to address the concerns raised by the EMA alert. There were two key areas in addressing the concerns highlighted. Firstly, clinicians had an heightened awareness of the potnetial risk of VTE and JAK inhibitor useage. Additionally, there was also the introduction of a new screening process which focussed on highlighting and assessing risk facotrs for VTE in patients being screened for JAK inhibitors.This was a new departmental service innovation introduced following the potential patient safety alert.We would postulate that some of the highly encouraging data obtained may partly be influenced by this service development. Conversely, much of the data was gathered before these assocations were established and before any service changes were made.We acknowedge that this data set is from a single centre analysis. However, given the sample size and duration of retrosepctive review we hope this serves to reassure clinicians that JAK inhibitor usage should remain a valid treatment option in Rheumatology patients, for licenced indications.