P107 Real world clinical outcomes of patients with moderate-to-severe rheumatoid arthritis initiating upadacitinib in the United Kingdom: Interim analysis from a prospective observational cohort study (ENDEAVOUR)
Authors: Taylor James , Srirangan Srinivasan , Bukhari Marwan , Bilgrami Syed , Nisar Muhammad K , McDonald Stephen , Goodson Nicola , Allard Andrew , Kinder Alison , Green Michael , Hunt Laura , Raizada Sabrina , Kirkham Bruce , Thomas Eleri , Horsfall Rachel , Bartlett Sean , Millward Rachael , Burton Victoria , Galloway James 
Published: April 2024

Abstract

Background/Aims
Upadacitinib (UPA) 15 mg, a once-daily Janus kinase inhibitor (JAKi), is approved by NICE for treating adults with moderate-to-severe rheumatoid arthritis (RA) unresponsive to conventional Disease Modifying Antirheumatic Drugs (DMARDs). This study aims to evaluate UPA's real-world effectiveness in the UK.

Methods
ENDEAVOUR is a prospective observational cohort study which recruited 97 patients with moderate to severe RA whom the managing health care professional has decided to treat with UPA in line with marketing authorisation across 14 sites in the UK. Patient demographics, comorbidities, concomitant therapies and patient reported disease activity were collected at baseline, three months, and six months. Patient Reported Outcomes (PROs) were collected using an app hosted by UMotif. Primary objective was the proportion of patients achieving clinical remission (defined as DAS28&lt;2.6) with upadacitinib at six months. The study is ongoing and therefore not all patients have completed study visits at three and six months yet however this interim analysis reports the baseline demographics of 77 patients whose data has been cleaned thus far and clinical outcomes and safety of UPA 47 adult patients at three months. Data are as observed.

Results
Data were available for 77 adults at baseline: 42% had moderate and 58% had severe RA based on DAS28-CRP scores. Patients' average age was 55 years, 64 (83%) were female, and most had at least one comorbidity, such as hypertension (16,21%) or asthma (12,16%). 32 (42%) had prior biologic therapy, with treatment failure the most commonly reported reason for switch (26/33, 79%). Of the 47 participants with three-month data, 18 (38%) achieved DAS28 remission. The proportion of patients with high disease activity decreased markedly from 45 (58%) at baseline to three (6%) at three months and moderate disease activity from 32 (42%) at baseline to 14 (30% at three months). Concurrent corticosteroid use declined, from 13 (17%) patients at baseline to just three (5%) by three months. The mean exposure time was six months (IQR five to seven).
Nine patients (9%) stopped UPA during the study period, (5/9 due to adverse events, 4/9 due to patient or physician choice). One case of shingles occurred, with temporary treatment interruption. Reports of serious adverse events were low (4% patients of events reported) with cases of serious and opportunistic infections reported most frequently (three cases). There were no reports of MACE or venous thromboembolic events. 1 report of malignancy (extranodal marginal zone B-cell lymphoma) was considered unrelated to treatment.

Conclusion
This preliminary analysis of an observational study provides valuable insights into the real-world effectiveness of UPA for treatment of moderate to severe RA with similar early efficacy to that observed in clinical trials. 38% of patients achieved clinical remission by 3 months, and adverse events were infrequent.

Disclosure
J. Taylor: None. S. Srirangan: None. M. Bukhari: Honoraria; M.B has received honoraria for speaking and attended advisory boards with Bristol-Myers Squib, UCB celltech, Roche/Chugai, Pfizer, AbbVie, Merck, Mennarini, Sanofi-aventis, Eli-Lilly, Janssen, Amgen, Novartis and Gilead. Other; M.B. has been sponsored to attend regional, national and international meetings by UCB celltech, Roche/Chugai, Pfizer, Abbvie, Merck, Mennarini, Janssen, Bristol-Myers Squib, Novartis and Eli-lilly. S. Bilgrami: Other; S.B. has received professional and financial support from Eli Lilly, UCB & Pfizer. M.K. Nisar: Other; M.K.N undertakes clinical trials and received support (including attendance at conferences, speaker fees and honoraria) from Roche, Chugai, MSD, AbbVie, Pfizer, BMS, Novartis, Celgene, UCB and, Lilly. S. McDonald: None. N. Goodson: None. A. Allard: Other; A.A. has received payment for services, sponsorship, funding, grants or worked on clinical trials for AbbVie, Eli Lilly, Pfizer, Novartis, BMS, Roche. A. Kinder: None. M. Green: None. L. Hunt: None. S. Raizada: Honoraria; S.R. has received honoraria from AbbVie. B. Kirkham: Consultancies; B.K. has received consultant/speaker fees from AbbVie, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer and UCB. Grants/research support; B.K. has received research support from Eli Lilly and Novartis. E. Thomas: Other; E.T. has been on advisory boards for Janssen and Galapagos. R. Horsfall: None. S. Bartlett: None. R. Millward: None. V. Burton: None. J. Galloway: Consultancies; J.G. has received speaker/consultancy for AbbVie, Galapagos, Janssen, Lilly, Pfizer, UCB and Vifor. Grants/research support; He has received research grants for AbbVie, Galapagos, GSK, Janssen, Lilly, Pfizer.