¹Ahmed S Zayat, ¹Abduljalil Mohamad Alragheb, ²Abdulrazzakh Poil, ³Kawther Ghassan Bohuliga, ⁵Nadeen Kalantan, ⁴Samah Allam, ⁹Sehriban Diab, ⁷Suzan Attar, ⁸Suad Hannawi, ²Samar Alemadi,

¹University of Sharjah, ²Hamad Medical cooperation, ³King Saud University, ⁴Alqasmi Hospital- Emirates Health Services, ⁵Alnoor Specialist Hospital,, ⁶Cleveland Clinic Abu Dhabi, ⁷King Abdulaziz University, ⁸Alkuwait-Dubai Hospital, Emirates Health Services, ⁹Sheikh Shakhbout Medical City, ¹⁰

Purpose Statement: Since the oral surveillance study, there has been potential concern about the use of JAK inhibitors (JAK-i) in high-risk patients and the elderly (1).  Some other registries have slightly different conclusions (2).  This could be potential hindrance for clinicians who are considering JAK-i in high-risk patients who either failed or contraindicated to have alternative advanced therapies. Furthermore, it is unclear if different JAK-i with different JAK selectivity have different potential risks and adverse events.  Similarly, there is limited data on the potential adverse events and risks in patients in the Middle East region and among the Arab population.

The primary objective of this study was to describe the variations in adverse events reported among the three different JAK-I, each exhibiting distinct levels of selectivity.  Other objectives were to assess the incidence rate of JAK-i adverse events in the Middle East and to investigate whether or not it is similar to the previously signaled adverse events such as herpes zoster infection, venous thromboembolism (VTE), MACEs, malignancy, and mortality.

Method(s): We used registry data of patients from 8 tertiary centers in Saudi Arabia, United Arab Emirates and Qatar (GULF-JAK study).  Data were collected retrospectively for all patients who received tofacitinib, baricitinib or upadacitinib over the past 8 years. Patients were startified into MACE risk group (50 years of age or older and had at least one additional cardiovascular risk factor) and MACE Non-risk group and VTE risk group (previous VTE).  The Incidence rate (IR) per 100 patient-year [95%CI] were calculated. Data analysis was conducted using SPSS 29. Descriptive and inferential statistics were used, as appropriate to the type of data. Level of significance was set at 5%.

Result(s): Registery data of 459 patients, who received JAK inhibitors were analysed in the study.  53.4%, 22.7%, 24.0% received tofacitinib, baricitinib and upadacitinib respectively.  In the cohort 263 (57.3%) were 50 years and older and 180(39.2%) were MACE risk group.  Major Adverse events were reported in 35 (7.7%) of patient on JAKi including 12 (4.9 %) on tofacitinib 6 (5.9%) on baricitinib and 17 (15.6%) on upadacitinib) (p 0.002).  Among the registry patients 25.1%, 32% 30.1%, 3.7% were diabetic, hypertensive, hyperlipidaemic or smokers respectively. Of all the patients, 26 (5.7%) were known to have IHD, 3 (0.7%) had VTE, 22 (4.8%) had chronic kidney disease (CKD) and 16 (3.5%) had history of malignancy prior to initiating JAKi.

In the cohort only 1 patient (0.2%) suffered VTE. Herpes Zoster (HZ) was reported in 14 (3.1%) patients (2.9%, 3%, 3.7% for tofacitinib, baricitinib and upadacitinib respectively) and none was ophthalmic or more than one dermatome. In the cohort 8(1.7%) patient were diagnosed with malignant cancer after initiating JAKi (3(1.2%), 3(3%) and 2(1.8%) patients on tofacitinib, baricitinib and upadacitinib respectively) all were among patient who were 50 years old and older.  Among the new cancer patients 4(50%) did have a history previous malignancy (p 0.001).

In the Cohort, 5 (1.1%) patient suffered MACE after initiating JAKi (1 (1%), 1 (0.8%) and 2 (1.8%) of Tofacitinib, Baricitinib and Upadacitinib respectively).  All events were in MACE risk-group; (5 (2.8%) of MACE risk-group)  patient suffered MACE after initiating JAKi. Generally, 40 (8.8%) patients were hospitalised due to potential AE across JAKi (6.2%, 12.9% and 11% for Tofacitinib, Baricitinib and Upadacitinib respectively).  6 (1.3%) patient died(1.2%, 1% and 1.8% for Tofacitinib, Baricitinib and Upadacitinib respectively).

Conclusion(s): Among the Arab population of the Middle East there appear to be a low incidence of VTE, MACE and HZ.  There was no events of MACE in low risk group patients.  More patient were diagnosed with malignancy who had previous malignant cancer.  The cohort data showed some differences in the rate of the adverse events between different JAKi with different selectivity which need to be confirmed in head to head randomised clinical trials.