BIMEKIZUMAB IMPACT ON CARDIOVASCULAR INFLAMMATION MARKERS IN MODERATE TO SEVERE PLAQUE PSORIASIS: RESULTS FROM PHASE 3 TRIALS

Background: High levels of inflammatory markers, such as neutrophil/lymphocyte ratio (NLR) and C-reactive protein (CRP), are observed in patients with psoriasis and are associated with poor cardiovascular (CV) outcomes.[1-3] Systemic anti-inflammatory therapies, including interleukin (IL)-17 blockade with secukinumab (SEC) or bimekizumab (BKZ), may reduce levels of CV inflammation-associated markers and, consequently, lower mortality risk in patients with psoriasis.[4] Dual inhibition of IL-17A and IL-17F with BKZ has shown efficacy in patients with moderate to severe plaque psoriasis.[5,6] Objectives: To assess the impact of BKZ on CV inflammation-associated markers versus (vs) placebo (PBO) over 16 weeks in the phase 3 BE VIVID trial, and vs SEC over 48 weeks in the phase 3b BE RADIANT trial. Methods: In BE VIVID, patients were randomised to BKZ 320 mg every 4 weeks (Q4W), PBO to Week 16 followed by BKZ Q4W, or ustekinumab to Week 52. In BE RADIANT, patients were randomised to BKZ 320 mg Q4W to Week 16 followed by BKZ Q4W or every 8 weeks (Q8W), or SEC 300 mg weekly to Week 4 then Q4W, to Week 48.[6] In BE VIVID, NLR was assessed to Week 16; CRP concentration was not systematically collected. In BE RADIANT, both NLR and CRP concentration were assessed. Median observed results are reported to Week 16 for BKZ Q4W- and PBO-randomised patients only from BE VIVID, and to Week 48 for BKZ- and SEC-randomised patients grouped by baseline CRP level (overall, CRP <5 mg/L, CRP ≥5 mg/L) from BE RADIANT (BKZ-randomised patients are presented as BKZ Total: combined BKZ Q4W and Q8W maintenance doses). Results: In BE VIVID, 321 patients were randomised to BKZ 320 mg Q4W and 83 to PBO. Median baseline neutrophil and lymphocyte concentrations were similar for BKZ Q4W and PBO patients ( Table 1 ). At Week 16, median NLR was reduced from baseline with BKZ Q4W and was lower with BKZ Q4W vs PBO: baseline, 2.54 vs 2.55; Week 16, 2.07 vs 2.53 ( Table 1 ). In BE RADIANT, 373 patients were randomised to BKZ and 370 to SEC. Median baseline neutrophil and lymphocyte concentrations were similar for BKZ- and SEC-randomised patients ( Table 2 ). Median NLR was reduced at Week 16 vs baseline with BKZ and SEC ( Table 2 ). NLR was comparable at baseline and Week 16 with BKZ Total vs SEC: baseline, 2.44 vs 2.37; Week 16, 2.07 vs 2.04 ( Table 2 ). These results were maintained to Week 48: 2.15 vs 2.07. Similar reductions in NLR from baseline to Week 16 were observed in subgroups of patients with baseline CRP <5 mg/L and CRP ≥5 mg/L, with both BKZ and SEC, in BE RADIANT. Median CRP concentrations (mg/L) were reduced at Week 16 vs baseline with BKZ and SEC ( Table 2 ). Week 16 CRP was comparable with BKZ Total vs SEC: 2.04 vs 2.04. These results were maintained to Week 48: 1.96 vs 2.03. Similar trends were observed in those with baseline CRP <5 mg/L and CRP ≥5 mg/L. Conclusion: BKZ treatment was associated with rapid, stable reductions in CV inflammation-associated biomarkers. At Week 16, NLR was reduced with BKZ vs PBO, and NLR and CRP concentrations were reduced vs baseline in both BKZ and SEC groups, particularly in patients with high CRP at baseline. Both markers remained stable through 1 year of BKZ or SEC treatment. REFERENCES: NIL. [1] Angkananard T et al. Biomed Res Int 2018;2703518. [2] Løfblad L et al. Sci Rep 2021;11:15644. [3] Aktaş Karabay E et al. Ann Dermatol 2019;31:601–10. [4] Terui H and Asano Y. J Clin Med 2023;12:1162. [5] Reich K et al. Lancet 2021;397:487–98, NCT03370133. [6] Reich K et al. N Engl J Med 2021;385:142–52, NCT03536884. Acknowledgements: Funding: Study funded by UCB Pharma. Medical writing support by Costello Medical. Disclosure of Interests: Georgios Kokolakis Received travel grants or honoraria, or has been a consultant member of advisory boards and speaker bureaus or has served as investigator for AbbVie, Actelion, Almirall, Amgen, Basilea, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Hexal-Sandoz, Janssen-Cilag, LEO Pharma, Eli Lilly and Company, MSD, Novartis, Pfizer, Sanofi, Takeda and UCB Pharma, Richard B. Warren Consulting fees from AbbVie, Almirall, Amgen, Arena, Astellas, Avillion, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, GSK, Janssen, LEO Pharma, Novartis, Pfizer, Sanofi, and UCB Pharma, Research grants to his institution from AbbVie, Almirall, Janssen, LEO Pharma, Novartis, and UCB Pharma; honoraria from Astellas, DiCE, GSK, and Union, Richard G. Langley Principal investigator for AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, LEO Pharma, Merck, Novartis, Pfizer and, UCB Pharma, Served on scientific advisory boards for AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, LEO Pharma, Merck, Novartis, Pfizer, and UCB Pharma; provided lectures for AbbVie, Amgen, Celgene, Eli Lilly, LEO Pharma, Merck, Novartis, and Pfizer, Brian Kirby Has been on scientific advisory boards for AbbVie, Almirall, Celgene, Eli Lilly, Janssen, MoonLake, Novartis, Pfizer, and UCB Pharma, Has been a consultant for AbbVie, Almirall, Celgene, Janssen, Merck, MoonLake, Novartis, Pfizer, and UCB Pharma; has received honoraria from AbbVie, Almirall, Celgene, Eli Lilly, Janssen, MoonLake, Novartis, Pfizer, and UCB Pharma, Received research support from or been a principal investigator (clinical trials) for AbbVie, Almirall, Janssen, Merck, MoonLake, Novartis, Pfizer, and UCB Pharma, James G. Krueger Personal fees from AbbVie, Aclaris, Allergan, Almirall, Amgen, Arena, Aristea, Asana, Aurigne, BiogenIdec, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Escalier, Galapagos, LEO Pharma, Menlo, Nimbus, Novartis, Pfizer, Sanofi, Sienna, Sun Pharma, UCB Pharma, Valeant, and Ventyx Biosciences, Grants paid to institution from AbbVie, Amgen, Akros, Allergan, Avillion, Biogen MA, Boehringer Ingelheim, Botanix, Bristol Myers Squibb, Celgene, Eli Lilly, Exicure, Incytem, Innovaderm, Janssen, LEO Pharma, Novan, Novartis, Pfizer, Paraxel, Regeneron, Sienna, UCB Pharma, and Vitae, Kilian Eyerich Speaker and/or advisor for AbbVie, Almirall, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Janssen, LEO Pharma, Pfizer, Novartis, Sanofi, and UCB Pharma, Leah Davis Shareholder of UCB Pharma, Employee of UCB Pharma, Owen Davies Employee of UCB Pharma, Nancy Cross Shareholder of UCB Pharma, Employee of UCB Pharma, Delphine Deherder Shareholder of UCB Pharma, Employee of UCB Pharma, Bruce Strober Speaker for AbbVie, Arcutis, Dermavant, Eli Lilly, Incyte, Janssen, Regeneron, and Sanofi Genzyme, Stock options from Connect Biopharma, Mindera Health; speaker for AbbVie, Arcutis, Dermavant, Eli Lilly, Incyte, Janssen, Regeneron, and Sanofi Genzyme, Consultant (honoraria): AbbVie, Acelyrin, Alamar, Almirall, Alumis, Amgen, Arcutis, Arena, Aristea, Asana, Boehringer Ingelheim, Bristol Myers Squibb, Capital One, Celltrion, CorEvitas, Dermavant, Eli Lilly, Imagenebio, Janssen, Kangpu Pharmaceuticals, Leo, Maruho, Meiji Seika Pharma, Protagonist, Monte Carlo, Novartis, Pfizer, Rapt, Regeneron, Sanofi-Genzyme, SG Cowen, Sun Pharma, Takeda, UCB Pharma, Union Therapeutics, Ventyxbio, and vTv Therapeutics. Scientific Co-Director (consulting fee): CorEvitas Psoriasis Registry; investigator for CorEvitas Psoriasis Registry; editor-in-chief (honorarium): Journal of Psoriasis and Psoriatic Arthritis. DOI: 10.1136/annrheumdis-2024-eular.2992 Keywords: Cardiovascular diseases, Clinical Trial, Comorbidities, Skin, Biomarkers Citation: , volume 83, supplement 1, year 2024, page 1459Session: Psoriatic arthritis (Publication Only)

Cardiovascular diseases, Clinical Trial, Comorbidities, Skin, Biomarkers