THU0169 JANUS KINASE INHIBITORSDEMONSTRATE EFFECTIVENESS IN A REAL-WORLD MULTI-BIOLOGIC DMARD REFRACTORY RHEUMATOID ARTHRITIS POPULATION
Authors: John Fitton, Andrew Melville, Shouvik Dass, Paul Emery, Jacqueline Nam, Maya Buch
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> The Janus Kinase inhibitors (JAKi) Tofacitinib and Baricitinib are licensed for use in Rheumatoid arthritis (RA). Trials in refractory RA (inefficacy and/or toxicity) to date (1, 2) suggest targeting intracellular signalling molecules and interrupting downstream effects of multiple cytokines may confer benefit in the management of patients who have failed multiple targeted therapies. <h3>Objectives</h3> To evaluate safety and efficacy of JAKi in a real-world population, including response in multi-bDMARD refractory RA. <h3>Methods</h3> We evaluated RA patients who had failed at least 2 csDMARD +/- one or more bDMARD, who were commenced on a JAKi. Patients who commenced Tofacitinib on a compassionate use programme in 2014 have been included (with Baricitinib available since February 2018). <h3>Results</h3> Seventy seven RA patients (80% female; mean (SD) age 55.9 (12.52) years) have been treated with one (or more) JAKis; 38 have received Tofacitinib and 39 Baricitinib (5 both). Table 1 details treatment stage and clinical outcomes where available (majority pending assessments). Number of previous bDMARD was higher in the Tofacitinib group (reflecting compassionate access scheme). Of the 38 patients who received Tofacitinib, 24 stopped treatment, 10 due to primary non-response, 2 secondary non-response and 12 due to adverse effects (1 deranged LFTs, 3 infection, 1 rash, 1 headache, 2 flares of IBD, 1 dizziness, 1 malignancy). Despite the refractory nature of their RA, 14 patients responded sufficiently to remain on Tofacitinib for an average of 24.5 months to date. 1 Patient who failed 3 bDMARDs achieved remission (DAS28 1.82) with 4 confirmed as having moderate disease activity (Mean DAS 3.58, SD 0.42). Of the 39 patients to receive Baricitinib, three had primary non-response, whilst the others remain on therapy. Response is to be determined in 16, 4 have achieved remission (Mean DAS 2.2, SD 0.32) and 14 MDA (Mean DAS 4.04, SD 0.44). 5 patients received both JAKis sequentially, switching from Tofacitinib to Baricitinib, 2 due to adverse events (both flares of IBD) and 3 due to non-response. Of these 5, 1 patient to date has shown a good response at 3 months, 2 have shown no response, with results pending for others. <h3>Conclusion</h3> Our experience of patients treated with JAKi for RA indicates improvement in disease activity. Benefit was observed in a severely refractory subgroup that had previously failed multiple biologic therapies. <h3>References</h3> [1] Genovese, M.C. et al. Response to baricitinib based on prior biologic use in patients with refractory rheumatoid arthritis. Rheumatology (Oxford). 2018, 57(5), pp.900-908. [2] Genovese, M.C. et al. Baricitinib in Patients with Refractory Rheumatoid Arthritis. N Engl J Med. 2016, 374(13), pp.1243-52. <h3>Disclosure of Interests</h3> John Fitton: None declared, Andrew Melville: None declared, Shouvik Dass: None declared, Paul Emery Grant/research support from: Pfizer, MSD, AbbVie, Bristol-Myers Squibb, Roche, Consultant for: Pfizer, MSD, AbbVie, Bristol-Myers Squibb, UCB, Roche, Novartis, Gilead,Samsung, Sandoz and Lilly, Jacqueline Nam: None declared, Maya Buch Grant/research support from: Pfizer LTD, UCB, Consultant for: AbbVie, Eli Lilly, EMD Serono, Pfizer Ltd., Sanofi