Correlation of changes in inflammatory and collagen biomarkers with durable guselkumab efficacy through 2 years in participants with active psoriatic arthritis: results from a phase III randomized controlled trial.
| Autor: | Siebert S; School of Infection & Immunity, University of Glasgow, Sir Graeme Davies Building, 4th Floor, 120 University Place, Glasgow G12 8TA, UK., Schett G; Department of Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany., Raychaudhuri SP; Division of Rheumatology, Allergy and Clinical Immunology, University of California Davis, School of Medicine, Sacramento, CA, USA.; VA Northern California Health Care System, Mather, CA, USA., Guma M; Division of Rheumatology, Autoimmunity and Inflammation, Department of Medicine, University of California San Diego, La Jolla, CA, USA., Chen W; Immunology, Janssen Research & Development, LLC, Spring House, PA, USA., Gao S; Immunology, Janssen Research & Development, LLC, Spring House, PA, USA., Chakravarty SD; Immunology, Janssen Scientific Affairs, LLC, a Johnson & Johnson Company, Horsham, PA, USA.; Division of Rheumatology, Drexel University College of Medicine, Philadelphia, PA, USA., Lavie F; Immunology Global Medical Affairs, Janssen Cilag Global Medical Affairs, Issy les Moulineaux, France., Rahman P; Craig L. Dobbin Genetics Research Centre, Discipline of Medicine, Division of Rheumatology, Memorial University of Newfoundland, St John's, Canada. |
|---|---|
| Jazyk: | angličtina |
| Zdroj: | Therapeutic advances in musculoskeletal disease [Ther Adv Musculoskelet Dis] 2024 Oct 27; Vol. 16, pp. 1759720X241283536. Date of Electronic Publication: 2024 Oct 27 (Print Publication: 2024). |
| DOI: | 10.1177/1759720X241283536 |
| Abstrakt: | Background: Guselkumab (human monoclonal antibody) selectively inhibits the interleukin (IL)-23p19 subunit. Objectives: Assess the longer-term pharmacodynamic effects of guselkumab and explore associations between such effects and clinical responses in patients with active psoriatic arthritis (PsA). Design: DISCOVER-2 randomized 739 biologic-naïve patients with active PsA (swollen/tender joint counts each ⩾5, C-reactive protein (CRP) ⩾0.6 mg/dL) to guselkumab (100 mg every 4 weeks (Q4W) or at Weeks 0, 4, and then Q8W) or placebo. Guselkumab-randomized participants with available serum biomarker data (randomly selected to reflect demographic and disease characteristics of the DISCOVER-2 population) comprised inflammatory ( N = 100) and collagen ( N = 178) biomarker cohorts. Methods: Pharmacodynamic effects of guselkumab through 2 years on inflammatory and collagen biomarker levels (general linear model) and associations between biomarkers and improvements in composite measures of joint, skin, and overall disease activity (Spearman linear regression) through 2 years were assessed. The relationship between the pharmacodynamic effects of guselkumab and achieving ⩾50% improvement in the American College of Rheumatology response criteria (ACR50) was assessed using a general linear model. Results: With guselkumab, pharmacodynamic effects on inflammatory (CRP, IL-6, serum amyloid A (SAA), IL-17A, IL-17F, IL-22, and beta-defensin 2 (BD-2)) and collagen (matrix metalloproteinase-degradation type I, III, IV, and VI collagen (C1M, C3M, C4M, and C6M)) biomarker levels were sustained or enhanced through Week 100. Throughout follow-up timepoints (Week 24/52/100), decreases in CRP, IL-6, C1M, and C6M levels correlated ( r = 0.26-0.30; p < 0.05) with improved joint disease activity (Disease Activity in Psoriatic Arthritis); decreases in IL-17A, IL-17F, IL-22, and BD-2 levels correlated ( r = 0.34-0.58; p < 0.05) with improved skin disease (Psoriasis Area and Severity Index); and decreases in C1M, C3M, C4M, and C6M correlated ( r = 0.27-0.31; p < 0.05) with improved overall disease activity (Psoriatic Arthritis Disease Activity Score). Significantly ( p < 0.05) greater reductions from baseline at Week 100 in CRP, IL-6, SAA, and C1M levels were observed in participants improving from Week 24 ACR50 nonresponse to Week 100 ACR50 response and were accompanied by a significant decrease in C1M from Week 24 to Week 100 versus nonresponders at both Weeks 24 and 100. Conclusion: In biologic-naïve participants with active PsA, guselkumab elicited substantial and enduring reductions in biomarkers that were associated with durable improvements in joint, skin, and overall disease activity through 2 years of DISCOVER-2. Trial Registration: NCT03158285 (clinicaltrials.gov identifier). Competing Interests: SS: research support from Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, and UCB; honoraria/speaker fees from AbbVie, Amgen, AstraZeneca, Eli Lilly, GlaxoSmithKline, Janssen, Teijin Pharma, and UCB. GS: speaker fees from Janssen and Novartis. SPR: research support, consulting fees, and/or speaker fees from AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, SUN, and UCB. MG: research support and/or consulting fees from Genentech, Gilead, Novartis, Pfizer, and Sonoma Biotherapeutics. WC and SG: employees of Janssen Research & Development, LLC; own stock or stock options in Johnson & Johnson. SDC: employee of Janssen Scientific Affairs, LLC, a Johnson & Johnson company; owns stock or stock options in Johnson & Johnson. FL: employee of Janssen Pharmaceutical Companies of Johnson & Johnson; owns stock or stock options in Johnson & Johnson. PR: Grant/research support from Janssen and Novartis; and consultant fees from Abbot, AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, and UCB. (© The Author(s), 2024.) |
| Databáze: | MEDLINE |
| Externí odkaz: |
|