Opportunistic infections associated with Janus kinase inhibitor treatment for rheumatoid arthritis: A structured literature review

Selective JAK-Inhibitors in Spondyloarthritis

“…In a recent structured literature review in RA, it was estimated that the overall exposure-adjusted incidence rate (EAIR) [per 100PY] for any form of HZ infection ranged from 1.1 to 12.3 per 100 PY for approved doses of all JAKis. 29 The EAIR was 12.3 for upadacitinib 15mg OD, 1.3 for patients treated with filgotinib 200mg OD with methotrexate and 1.5 in those receiving filgotinib monotherapy. 29 Along the same lines, data from the German RABBIT registry reported higher risk for HZ for JAKi and TNFi, compared to csDMARDs (HR: 1.66 and 1.63, respectively).…”

“… 29 The EAIR was 12.3 for upadacitinib 15mg OD, 1.3 for patients treated with filgotinib 200mg OD with methotrexate and 1.5 in those receiving filgotinib monotherapy. 29 Along the same lines, data from the German RABBIT registry reported higher risk for HZ for JAKi and TNFi, compared to csDMARDs (HR: 1.66 and 1.63, respectively). 37 A cohort retrospective study in an Asian population reported that the EAIR of HZ for JAKi was nearly double that for TNFi (11.54 and 4.88 per 100 PY, respectively) 30 while, a Japanese cohort study also noted an increased risk of HZ with JAKi compared with TNFi [TNFi vs JAKi HR for HZ: 0.200 (95% CI: 0.077, 0.524) p=0.001].…”

“…In a structured literature review, opportunistic infections associated with JAKi for treatment in patients with RA were evaluated. 29 Data and rates of opportunistic infections from 105 publications referring to 62 unique clinical trials were included. The most commonly reported opportunistic infection was reactivation of HZV leading to Zoster, whereas other opportunistic infections such as tuberculosis (TB), Pneumocystis Pneumonia (PCP), and candidiasis were reported more rarely.…”

“…Other rare opportunistic infections with a frequency of ≤1% included CMV (0.3%) reported with tofacitinib 5mg twice daily (BD), and aspergillosis (0.15%) and listeria monocytogenes infection (0.15%) reported with upadacitinib 15mg OD. 29 …”

Determination of Enantiomer in Tofacitinib Citrate Using Reversed-Phase Chiral High-Performance Liquid Chromatography

“…Tofacitinib citrate, 3-((3R,4R)-4-methyl-3-(methyl (7H-pyrrolo [2,3-d] pyrimidin-4yl) amino) piperidin-1-y1)-3-oxopropanenitrile, 2-hydroxy-1,2,3-propane tricarboxylate (Figure 1a), was the first janus kinase (JAK) inhibitor approved for the treatment of adult patients with moderate-to-severe rheumatoid arthritis (RA) who have had an inadequate response or intolerance to methotrexate [1][2][3][4]. It blocks the cascade amplification of cytokines by inhibiting the JAK1/3 dimer-mediated interleukin (IL)-2, 4, 7, 9, 15, 21, tumor necrosis factor (TNF) and interferon (IFN)-γ pathways, effectively reducing ground joint dysfunction in RA patients [5,6].…”