SAFETY OUTCOMES IN PATIENTS (PTS) WITH RHEUMATOID ARTHRITIS (RA) TREATED WITH FILGOTINIB (FIL) IN FILOSOPHY: INTERIM RESULTS FROM A PROSPECTIVE OBSERVATIONAL STUDY

BackgroundConsideration is needed when using Janus kinase (JAK) inhibitors to treat RA in pts aged ≥65 years or those with cardiovascular (CV) risk factors. The JAK1 preferential inhibitor FIL was generally well tolerated in clinical trials[1];safety has not been determined in a real-world setting.ObjectivesTo report baseline characteristics and up to 6-month safety data from the first 480 pts treated with FIL in the FILOSOPHY study (NCT04871919), and in two mutually exclusive subgroups based on age and CV risk.MethodsFILOSOPHY is an ongoing, phase 4, non-interventional, European study of pts with RA who have been prescribed FIL for the first time and in accordance with the product label in daily practice. Baseline characteristics and the incidence of select adverse events (AEs) are assessed in pts aged ≥65 years and/or with ≥1 CV risk factor (Table 1), and in those aged <65 years with no CV risk factors.ResultsAs of the end of June 2022, 480 pts had been treated: 441 received FIL 200 mg and 39 received FIL 100 mg. Of the 480 pts, 148 (30.8%) were aged ≥65 years;332 (69.2%) were aged <65 years. In total, 86 (17.9%) were former smokers, 81 (16.9%) were current smokers and 203 (42.3%) were non-smokers (data were missing for 110 pts [22.9%]). In addition to smoking, the most frequent CV risk factors included a history of hypertension (32.3%), a history of dyslipidemia (10.2%) and a family history of myocardial infarction (8.5%;Table 1).23 pts (4.8%) discontinued treatment due to AEs. Of the 354 pts aged ≥65 years or with ≥1 CV risk factor, infections affected 64 pts (18.1%), 34 (9.6%) had COVID-19, 2 (0.6%) had herpes zoster, and cardiac disorders (angina pectoris, atrial fibrillation, palpitations and tachycardia) affected 5 pts (1.4%);no cases of malignancies were observed. In the subgroup aged <65 years and with no CV risk factors (n=126), infections occurred in 18 pts (14.3%) (9 [7.1%] had COVID-19;3 [2.4%] had herpes zoster) and malignancies (myeloproliferative neoplasm) affected 1 pt (0.8%);no pts had cardiac disorders. There were no cases of deep vein thrombosis or pulmonary embolism in either subgroup.ConclusionIn this interim analysis of FILOSOPHY, no unexpected safety signals emerged at up to 6 months. Although infections and cardiac disorders affected a numerically greater proportion of pts aged ≥65 years or with ≥1 CV risk vs those aged <65 years with no CV risk, longer follow-up on a broader cohort is necessary to further characterize the safety of FIL in different groups of pts with RA.Reference[1]Winthrop K, et al. Ann Rheum Dis 2022;81:184–92Table 1.Baseline characteristics and CV risk factorsBaseline demographics/CV risk factorsAll FIL-treated pts (N=480)≥65 years or with ≥1 CV risk factor (n=354)<65 years and no CV risk factor (n=126)*Female sex, n (%)351 (73.1)252 (71.2)99 (78.6)Age, years, mean (SD)57.6 (11.5)60.4 (10.8)49.6 (9.6)Rheumatoid factor positive, n (%)†228 (47.5)167 (47.2)61 (48.4)Anti-citrullinated protein antibody positive, n (%)‡243 (50.6)176 (49.7)67 (53. 2)Body mass index, kg/m2, mean (SD)27.6 (5.7) n=43728.0 (5.4) n=33126.3 (6.4) n=106RA disease duration, years, mean (SD)10.4 (9.4) n=47810.5 (9.5) n=35310.0 (8.8) n=125Tender joint count 28, mean (SD)8.6 (6.9) n=4578.7 (7.1) n=3408.3 (6.3) n=117Swollen joint count 28, mean (SD)5.6 (5.2) n=4525.7 (5.4) n=3365.4 (4.4) n=116Former smoker, n (%)§86 (17.9)86 (24.3)0Current smoker, n (%)§81 (16.9)81 (22.9)0Non-smoker, n (%)§203 (42.3)130 (36.7)73 (57.9)Family history of myocardial infarction, n (%)41 (8.5)41 (11.6)0Medical history of: n (%) CV disease33 (6.9)33 (9.3)0 Diabetes35 (7.3)35 (9.9)0 Dyslipidemia49 (10.2)49 (13.8)0 Hypertension155 (32.3)155 (43.8)0 Ischemic CNS  vascular disorders11 (2.3)11 (3.1)0 Peripheral vascular disease17 (3.5)17 (4.8)0*Includes 53 pts with missing smoking status data who were aged <65 years with no other CV risk factors.†Missing/unknown in 154 pts;‡Missing in 153 pts;§Smoking status data missing in 110 pts (22.9%).AcknowledgementsWe thank the physicia s and patients who participated in this study. The study was funded by Galapagos NV, Mechelen, Belgium. Publication coordination was provided by Fabien Debailleul, PhD, of Galapagos NV. Medical writing support was provided by Debbie Sherwood, BSc, CMPP (Aspire Scientific, Bollington, UK), and funded by Galapagos NV.Disclosure of InterestsPatrick Verschueren Speakers bureau: AbbVie, Eli Lilly, Galapagos, Roularta, Consultant of: Celltrion, Eli Lilly, Galapagos, Gilead, Nordic Pharma, Sidekick Health, Grant/research support from: Galapagos, Pfizer, Jérôme Avouac Speakers bureau: AbbVie, AstraZeneca, BMS, Eli Lilly, Galapagos, MSD, Novartis, Pfizer, Sandoz, Sanofi, Consultant of: AbbVie, Fresenius Kabi, Galapagos, Sanofi, Grant/research support from: BMS, Fresenius Kabi, Novartis, Pfizer, Karen Bevers Grant/research support from: Galapagos, Susana Romero-Yuste Speakers bureau: AbbVie, Biogen, BMS, Lilly, Pfizer, Consultant of: Sanofi, Lilly, Grant/research support from: Lilly, MSD, Roberto Caporali Speakers bureau: AbbVie, Amgen, BMS, Celltrion, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, Sandoz, UCB, Consultant of: AbbVie, Amgen, BMS, Celltrion, Eli Lilly, Fresenius Kabi, Galapagos, Janssen, MSD, Novartis, Pfizer, Roche, Sandoz, UCB, Thomas Debray Consultant of: Biogen, Galapagos, Gilead, Francesco De Leonardis Employee of: Galapagos, James Galloway Speakers bureau: AbbVie, Biogen, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Roche, UCB, Consultant of: AbbVie, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Grant/research support from: AstraZeneca, Celgene, Gilead, Janssen, Medicago, Novavax, Pfizer, Monia Zignani Shareholder of: Galapagos, Employee of: Galapagos, Gerd Rüdiger Burmester Speakers bureau: AbbVie, Amgen, BMS, Chugai, Galapagos, Lilly, Pfizer, Sanofi, Consultant of: AbbVie, Amgen, BMS, Galapagos, Lilly, Pfizer, Sanofi.

Ethics committee experience during COVID-19 emergency. a brief report

Background: The health crisis caused by COVID-19 required the prompt launch of research in order to generate scientific evidence pertaining to the new disease oriented to control its devastating effects and continuous spread. Therefore, it was essential to adapt the work flow of Research Ethics Committees, to prioritize and to accelerate the evaluation of projects related to this disease.

[Ethics Committee experience during COVID-19 emergency. A brief report.]

OBJECTIVE: The health crisis caused by COVID-19 required the prompt launch of research in order to generate scientific evidence pertaining to the new disease oriented to control its devastating effects and continuous spread. Therefore, it was essential to adapt the work flow of Research Ethics Committees, to prioritize and to accelerate the evaluation of projects related to this disease. METHODS: This work analyses the evaluation conducted by our Regional Ethics Committees during the initial period of the health emergency (between 13th March and 28th May 2020). RESULTS: 81 research projects were evaluated, 73 of them of regional scope (62 single-centre), 4 national and 4 international. 57 projects obtained a favourable opinion, 4 were withdrawn by the sponsors, 6 did not require ethics approval and 14 did not respond to the clarifications requested up to the date of the study's closure. CONCLUSIONS: The most important research procedures to be analysed in this context are those related to the methodology and informed consent process. It is also essential to address aspects related to the privacy of personal data, and to take into account the workload of the researchers. As an improvement proposal, we think that greater collaboration between the different research teams should be encourage to obtain more robust results.