Abstract
Objective. To report pharmacokinetics (PK), immunogenicity, clinical effect, and safety of intravenous (IV) golimumab in children with active polyarticular-course juvenile idiopathic arthritis (pcJIA) who participated in A Study to Evaluate the Pharmacokinetics, Efficacy and Safety of Intravenous Golimumab in Pediatric Participants With Active Polyarticular Course Juvenile Idiopathic Arthritis Despite Methotrexate Therapy (GO-VIVA)’s open-label, long-term extension (LTE) through week 252. Methods. GO-VIVA participants who continued IV golimumab (80 mg/m2 every 8 weeks) after week 52 were included. PK and safety were assessed through week 244 (last dose) and week 252, respectively, and clinical response through week 116. Clinical outcomes included JIA–American College of Rheumatology (ACR) responses and clinical Juvenile Arthritis Disease Activity Score in 10 joints (cJADAS10). Binary outcomes used nonresponder imputation, and other descriptive analyses used observed data. Results. Of 112/127 (88.2%) participants entering the LTE, 69 completed the week 252 visit. Median steady-state trough golimumab concentrations were generally maintained from week 52 through week 244 (range 0.3-0.6 μg/mL). Antigolimumab antibody rates were consistent through week 52 (39.2% [49/125]) and week 244 (44.8% [56/125]). Week 52 JIA-ACR 30/50/70/90 response rates (75.6% [96/127], 74% [94/127], 65.4%[83/127], and 48.8%[62/127], respectively) were generally maintained through week 116(72.4%[92/127], 71.7% [91/127], 63.8% [81/127], and 50.4% [64/127], respectively), when the median cJADAS10 was 1.6 and 56.7% (72/127) of participants achieved cJADAS10 ≤ 5 (minimal disease activity). Rates (per 100 patient-years) of serious adverse events and serious infections through week 252 were 7.7 and 3.9, respectively. Conclusion. GO-VIVA LTE participants experienced adequate PK exposure and stable safety and immunogenicity. The majority of participants experienced no more than minimal residual disease activity. Data suggest IV golimumab treatment provided durable clinical response through week 116, with an acceptable risk-benefit profile.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1125-1134 |
| Number of pages | 10 |
| Journal | Journal of Rheumatology |
| Volume | 51 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 1 2024 |
Funding
This study was sponsored by Janssen Research and Development, LLC. The authors thank all PRINTO and PRCSG center personnel and all families who contributed to the study. Medical writing support was provided by Holly Capasso-Harris of Certara, under the direction of the authors and the guidance of PRINTO and PRCSG officers (NR, DJL, HIB, AM) in accordance with Good Publication Practice guidelines (Ann Intern Med 2022;175:1298-1304) and was funded by Janssen Research and Development, LLC. Center, Division of Pediatric Rheumatology, New Hyde Park, New York, USA; 15D.M. Levy, MD, MS, The Hospital for Sick Children (SickKids), Toronto, and the University of Toronto, Toronto, Ontario, Canada; 16C.E. Rabinovich, MD, Duke University, Durham, North Carolina, USA; 17C. Artur Silva, MD, Instituto da Crian\u00E7a e Adolescente, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de S\u00E3o Paulo, S\u00E3o Paulo, Brazil; 18Y. Spivakovsky, MD, Saratov State Medical University n.a. V.I. Razumovsky of Ministry of Health of the Russian Federation, Saratov, Russia; 19Y. Uziel, MD, Pediatric Rheumatology Unit, Department of Pediatrics, Meir Medical Center, Kfar-Saba, Tel Aviv School of Medicine, Tel Aviv University, Tel Aviv, Israel; 20S. Ringold, MD, MS, X.L. Xu, PhD, J.H. Leu, PharmD, PhD, E. Lam, PharmD, Y. Wang, PhD, Janssen Research and Development, LLC, Spring House, Pennsylvania, USA; 21A. Martini, MD, Universit\u00E0 degli Studi di Genova, Dipartimento di Neuroscienze, Riabilitazione, Oftalmologia, Genetica e Scienze Materno-Infantili (DiNOGMI), Genova, Italy; 22N. Ruperto, MD, MPH, IRCCS Istituto Giannina Gaslini, Servizio Sperimentazioni Cliniche Pediatriche/Gaslini Trial Centre, PRINTO, Genoa, Italy. HIB works as a full-time public employee at the Cincinnati Children\u2019s Hospital, which has received contributions from the following industries in the past 3 years: BMS, Eli Lilly, GSK, F. Hoffmann-La Roche, Janssen, Novartis, and Pfizer. This funding has been reinvested for the research activities of the hospital in a fully independent manner, without any commitment to third parties. HIB has also received consulting fees from AbbVie, AstraZeneca-Medimmune, Biogen, Boehringer Ingelheim, BMS, Celgene, Eli Lilly, EMD Serono, Genzyme, GSK, F. Hoffmann-La Roche, Janssen, Merck, Novartis, R-Pharm, and Sanofi, and has served on speakers\u2019 bureaus for Novartis, Roche, and GSK. CPT has received speaker fees from AbbVie, Boehringer Ingelheim, BMS, Eli Lilly, Janssen, Novartis, and Pfizer, and has served as a principal investigator for AbbVie, AstraZeneca, Biogen, Boehringer Ingelheim, Eli Lilly, Janssen, and UCB. IL has served as a consultant/advisory board member for AbbVie, Janssen, Lilly, and Pfizer. EA has received grant/research support from AbbVie, Amgen, BMS, Eli Lilly, MSD, Novartis, Pfizer, Roche, and Sanofi, and has been a speaker for AbbVie, BMS, MSD, Novartis, Pfizer, and Roche. SA has received consulting fees from AstraZeneca and GSK, and served as a principal investigator in clinical trials for BMS, Celgene, Eli Lilly, Janssen, Novartis, and Roche. AZ owns stock in Merck, OPKO Health, and Teva. DML has received consulting fees from Janssen and has served as a principal investigator for AstraZeneca, BMS, Roche, and Sobi. CER has received grant/research support (paid to institution) from AbbVie and UCB. YU has received speaker fees from AbbVie, Novartis, and Pfizer. SR, XLX, JHL, EL, and YW are employees of Janssen Research and Development, LLC, a wholly owned subsidiary of Johnson & Johnson, and may own stock or stock options in Johnson & Johnson. DJL has received grant/research support from BMS, Janssen Research and Development LLC, and Roche Laboratories; consulting fees from AstraZeneca, GSK, Novartis, Pfizer (consultant and advisory board member), and United Bioscience Corporation; and served on speakers\u2019 bureaus for Novartis and Pfizer (all above are paid to institution). AM has received consulting fees from AbbVie, Boehringer Ingelheim, Eli Lilly, EMD Serono, Idorsia, Janssen, Novartis, and Pfizer. NR received honoraria for scientific consultancies or speaker bureau participation in the past 2 years from AbbVie, Aclaris, Amgen, AstraZeneca, Aurinia, Boehringer Ingelheim, BMS, Eli Lilly, Galapagos, Guidepoint, Janssen, Novartis, Pfizer, and Sanofi. The remaining authors declare no conflicts of interest relevant to this article. Address correspondence to Dr. H.I. Brunner, Cincinnati Children\u2019s Hospital Medical Center, Division of Rheumatology, 3333 Burnet Avenue, Cincinnati, OH 45229, USA. Email: [email protected]. Accepted for publication July 16, 2024. The authors thank all PRINTO and PRCSG center personnel and all families who contributed to the study. Medical writing support was provided by Holly Capasso-Harris of Certara, under the direction of the authors and the guidance of PRINTO and PRCSG officers (NR, DJL, HIB, AM) in accordance with Good Publication Practice guidelines (Ann Intern Med 2022;175:1298-1304) and was funded by Janssen Research and Development, LLC. The authors also thank the following collaborators: Arturo Borzutzky, MD, Santiago, Chile; Ruben Cuttica, MD, Buenos Aires, Argentina; Liudmila Grebenkina, MD, Togliatti, Russia; Christi J. Inman, MD, Salt Lake City, Utah, USA; Vladimir Keltsev, MD, Togliatti, Russia (deceased); Daniel J. Kingsbury, MD, Portland, Oregon, USA; Victor Malievskiy, MD, Ufa, Russia; Taciana A. Pedrosa Fernandes, MD, Botucatu, Brazil; Maria del Rocio Maldonado Velazquez, MD, Mexico City, Mexico; Heinrike Schmeling, MD, Calgary, Canada; Christiaan Scott, MD, Cape Town, South Africa; Alberto Spindler, MD, San Miguel de Tucum\u00E1n, Argentina; Maria Teresa Terreri, MD, S\u00E3o Paulo, Brazil; Diego Oscar Viola, MD, Rosario, Argentina; Ricardo M. Xavier, MD, Porto Alegre, Brazil.
Keywords
- biological therapy
- disease-modifying antirheumatic drugs
- intravenous golimumab
- polyarticular-course juvenile idiopathic arthritis
ASJC Scopus subject areas
- Rheumatology
- Immunology and Allergy
- Immunology