PMID- 37747626 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20231119 IS - 2198-6576 (Print) IS - 2198-6584 (Electronic) IS - 2198-6576 (Linking) VI - 10 IP - 6 DP - 2023 Dec TI - Effect of Filgotinib on Body Mass Index (BMI) and Effect of Baseline BMI on the Efficacy and Safety of Filgotinib in Rheumatoid Arthritis. PG - 1555-1574 LID - 10.1007/s40744-023-00599-1 [doi] AB - INTRODUCTION: This post hoc analysis of the phase 3 rheumatoid arthritis (RA) filgotinib clinical trial program assessed the effect of filgotinib on body mass index (BMI) in patients with RA and the impact of BMI on the efficacy and safety of filgotinib. METHODS: FINCH 1-3 were randomized, double-blind, active- or placebo-controlled phase 3 trials of filgotinib 100 and 200 mg in patients with RA (N = 3452). BMI assessments included the mean change from baseline in BMI and the proportion of patients whose BMI increased by incremental thresholds. Efficacy measures included American College of Rheumatology (ACR) 20/50/70 response and low disease activity/remission according to Disease Activity Score 28 using C-reactive protein. The exposure-adjusted incident rate (EAIR) of adverse events (AEs) was assessed by baseline BMI, using integrated data from the FINCH 1-4 and the phase 2 DARWIN 1-3 studies (total filgotinib exposure = 8085 patient-years). RESULTS: Mean change from baseline in BMI over time was similar across treatment arms. In most patients, BMI increased by /= 4 kg/m(2). For most efficacy measures, filgotinib 200 mg was more efficacious than filgotinib 100 mg or active comparators or placebo across BMI subgroups. For the higher filgotinib dose, the EAIR of serious treatment-emergent AEs, venous thrombotic and embolic events, and major adverse cardiovascular events increased with increasing BMI. CONCLUSIONS: Filgotinib did not lead to substantial changes in BMI, and BMI did not appear to affect the efficacy of filgotinib. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT02889796, NCT02873936, NCT02886728, NCT03025308, NCT01888874, NCT01894516, NCT02065700. CI - (c) 2023. The Author(s). FAU - Balsa, Alejandro AU - Balsa A AUID- ORCID: 0000-0001-8070-7062 AD - Rheumatology Service, Hospital La Paz Institute for Health Research (IdiPAZ), Universidad Autonoma de Madrid, Paseo de la Castellana 261, 28046, Madrid, Spain. alejandro.balsa@salud.madrid.org. FAU - Wassenberg, Siegfried AU - Wassenberg S AD - Department of Rheumatology, Rheumazentrum Ratingen, Ratingen, Germany. FAU - Tanaka, Yoshiya AU - Tanaka Y AUID- ORCID: 0000-0002-0807-7139 AD - The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health Japan, Kitakyushu, Japan. FAU - Tournadre, Anne AU - Tournadre A AUID- ORCID: 0000-0002-5025-0214 AD - Rheumatology Service, Clermont Ferrand University Hospital, Clermont-Ferrand, France. FAU - Orzechowski, Hans-Dieter AU - Orzechowski HD AUID- ORCID: 0000-0001-7374-6899 AD - Medical Affairs, Galapagos Biopharma Deutschland GmbH, Munich, Germany. FAU - Rajendran, Vijay AU - Rajendran V AD - Clinical Research, Galapagos NV, Mechelen, Belgium. FAU - Lendl, Udo AU - Lendl U AD - Medical Affairs, Galapagos Biopharma Deutschland GmbH, Munich, Germany. FAU - Stiers, Pieter-Jan AU - Stiers PJ AD - Biostatistics, Galapagos NV, Mechelen, Belgium. FAU - Watson, Chris AU - Watson C AUID- ORCID: 0009-0007-9887-6092 AD - Medical Affairs, Galapagos Biotech Ltd, Cambridge, UK. FAU - Caporali, Roberto AU - Caporali R AD - Department of Clinical Sciences and Community Health, The University of Milan and ASST G. Pini-CTO Hospital, Milan, Italy. FAU - Galloway, James AU - Galloway J AUID- ORCID: 0000-0002-1230-2781 AD - Centre for Rheumatic Diseases, King's College London, London, UK. FAU - Verschueren, Patrick AU - Verschueren P AUID- ORCID: 0000-0002-0340-3580 AD - Department of Rheumatology, University Hospital Leuven, Leuven, Belgium. LA - eng SI - ClinicalTrials.gov/NCT02889796 SI - ClinicalTrials.gov/NCT02873936 SI - ClinicalTrials.gov/NCT02886728 SI - ClinicalTrials.gov/NCT03025308 SI - ClinicalTrials.gov/NCT01888874 SI - ClinicalTrials.gov/NCT01894516 SI - ClinicalTrials.gov/NCT02065700 PT - Journal Article DEP - 20230925 PL - England TA - Rheumatol Ther JT - Rheumatology and therapy JID - 101674543 PMC - PMC10654312 OAB - Some rheumatoid arthritis treatments cause patients to gain weight or are less effective in patients with obesity than in patients without obesity. Also, obesity can make rheumatoid arthritis worse. Filgotinib is a rheumatoid arthritis treatment that was evaluated in seven randomized clinical studies (FINCH 1-4 and DARWIN 1-3). We investigated whether filgotinib causes changes in weight and whether body mass index (BMI) affects the efficacy or safety of filgotinib. We analyzed how the BMI of patients who participated in FINCH 1, 2, or 3 changed over time. Most patients had a small increase in BMI (around 1-2 kg/m(2)) after 24 weeks of filgotinib treatment. This change in BMI was not affected by patients' BMI at baseline. Baseline BMI did not impact the efficacy of filgotinib, which was assessed using standard measures of disease activity. Filgotinib was more effective than other rheumatoid arthritis treatments and placebo in all patients, regardless of BMI subgroup. Using safety data from all seven clinical studies (FINCH 1-4 and DARWIN 1-3), we found that some adverse events occurred more often in patients with obesity (a BMI of >/= 30 kg/m(2)) than in those without obesity. The increased adverse events included venous thrombotic and embolic events and major adverse cardiovascular events, for which obesity is a known risk factor. These results show that filgotinib did not substantially change BMI (which increased by around 1-2 kg/m(2) in most patients), and that baseline BMI did not affect the efficacy of filgotinib. OABL- eng OTO - NOTNLM OT - Body mass index OT - Clinical trial OT - DMARD OT - Filgotinib OT - Interventional study OT - JAK inhibitor OT - Rheumatoid arthritis COIS- Alejandro Balsa has received grants/research support from AbbVie, Pfizer and UCB; worked as a paid consultant for AbbVie, Galapagos, Lilly, Nordic, Pfizer and UCB; and has been paid as a speaker for AbbVie, Galapagos, Gilead, Lilly, Nordic, Pfizer, Sandoz and UCB. Siegfried Wassenberg has received grants/research support from Pfizer; worked as a paid consultant for Galapagos, Lilly and UCB; and has been paid as a speaker for AbbVie, Medac, MSD and Pfizer. Yoshiya Tanaka received speaker fees and/or honoraria from AbbVie, AstraZeneca, Boehringer-Ingelheim, BMS, Chugai, Eisai, Eli Lilly, Gilead, GlaxoSmithKline, Pfizer, Taiho, and Taisho and received research grants from Chugai, Eisai, Mitsubishi-Tanabe Taisho. Anne Tournadre has received grants/research support from Novartis, Pfizer and UCB; worked as a paid consultant for AbbVie, Fresenius Kabi, Lilly, Novartis and Sanofi; and has been paid as an instructor for Fresenius Kabi, and as a speaker for Fresenius Kabi, Lilly, MSD and Sanofi. Hans-Dieter Orzechowski is a former employee of Galapagos and a shareholder in Gilead; Udo Lendl is an employee of Galapagos; Pieter-Jan Stiers is a former employee of Galapagos; Vijay Rajendran and Chris Watson are employees at, and shareholders in, Galapagos. Roberto Caporali worked as a paid consultant, and has been paid as a speaker, for AbbVie, Accord, BMS, Celltrion, Fresenius Kabi, Galapagos, Lilly, MSD, Novartis, Pfizer, Sandoz and UCB. James Galloway has worked as a paid consultant for AbbVie, Galapagos, Gilead, Janssen, Lilly, Novartis and Pfizer; has received grant/research support from AstraZeneca, Celgene, Gilead, Jansen, Medicago, Novavax and Pfizer; has received speaker fees/honoraria from AbbVie, Biogen, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche and UCB. Patrick Verschueren has received institutional grants/research support from Galapagos (Galapagos Chair in Rheumatoid Arthritis at KU Leuven, Belgium, outside the scope of the current study) and Pfizer (Pfizer Chair Management of Early Rheumatoid Arthritis at KU Leuven, Belgium); worked as a paid consultant for AbbVie, BMS, Celltrion, Eli Lilly, Galapagos, Gilead, Nordic Pharma, Pfizer, Sidekick Health and UCB; and has been paid as a speaker for Eli Lilly, Galapagos, MSD and Roularta. EDAT- 2023/09/25 12:41 MHDA- 2023/09/25 12:42 PMCR- 2023/09/25 CRDT- 2023/09/25 11:13 PHST- 2023/07/06 00:00 [received] PHST- 2023/09/05 00:00 [accepted] PHST- 2023/09/25 12:42 [medline] PHST- 2023/09/25 12:41 [pubmed] PHST- 2023/09/25 11:13 [entrez] PHST- 2023/09/25 00:00 [pmc-release] AID - 10.1007/s40744-023-00599-1 [pii] AID - 599 [pii] AID - 10.1007/s40744-023-00599-1 [doi] PST - ppublish SO - Rheumatol Ther. 2023 Dec;10(6):1555-1574. doi: 10.1007/s40744-023-00599-1. Epub 2023 Sep 25.