Absence of Association Between Abatacept Exposure and Initial Infection in Patients With Juvenile Idiopathic Arthritis

Nicolino Ruperto; Hermine I Brunner; Nikolay Tzaribachev; Gabriel Vega-Cornejo; Ingrid Louw; Rolando Cimaz; Jason Dare; Graciela Espada; Enrique Faugier; Manuel Ferrandiz; Valeria Gerloni; Pierre Quartier; Clovis Artur Silva; Linda Wagner-Weiner; Yash Gandhi; Julie Passarell; Marleen Nys; Robert Wong; Alberto Martini; Daniel J Lovell; Pediatric Rheumatology Collaborative Study Group (PRCSG) and the Paediatric Rheumatology International Trials Organisation (PRINTO)

doi:10.3899/jrheum.200154

Absence of Association Between Abatacept Exposure and Initial Infection in Patients With Juvenile Idiopathic Arthritis

J Rheumatol. 2021 Jul;48(7):1073-1081. doi: 10.3899/jrheum.200154. Epub 2021 Jan 15.

Authors

Nicolino Ruperto¹, Hermine I Brunner², Nikolay Tzaribachev³, Gabriel Vega-Cornejo⁴, Ingrid Louw⁵, Rolando Cimaz⁶, Jason Dare⁷, Graciela Espada⁸, Enrique Faugier⁹, Manuel Ferrandiz¹⁰, Valeria Gerloni¹¹, Pierre Quartier¹², Clovis Artur Silva¹³, Linda Wagner-Weiner¹⁴, Yash Gandhi¹⁵, Julie Passarell¹⁶, Marleen Nys¹⁷, Robert Wong¹⁵, Alberto Martini¹⁸, Daniel J Lovell; Pediatric Rheumatology Collaborative Study Group (PRCSG) and the Paediatric Rheumatology International Trials Organisation (PRINTO)

Affiliations

¹ N. Ruperto, MD, MPH, IRCCS Istituto G Gaslini, Clinica Pediatrica e Reumatologia-UOSID Centro Trial, Genoa, Italy; nicolaruperto@gaslini.org.
² H.I. Brunner, MD, MSc, MBA, D.J. Lovell, MD, MPH, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
³ N. Tzaribachev, MD, Pediatric Rheumatology Research Institute, Bad Bramstedt, Germany.
⁴ G. Vega-Cornejo, MD, CREA Hospital México Americano, Guadalajara, Jalisco, Mexico.
⁵ I. Louw, MMED, MBChB, Panorama Medical Centre, Cape Town, South Africa.
⁶ R. Cimaz, MD, University Hospital Meyer, Florence, Italy and Department of Clinical Sciences and Community Health, University of Milano, Milan, Italy.
⁷ J. Dare, MD, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
⁸ G. Espada, MD, Hospital de Niños Dr Ricardo Gutiérrez, Buenos Aires, Argentina.
⁹ E. Faugier, MD, Hospital Infantil de México Federico Gómez, Mexico City, Mexico.
¹⁰ M. Ferrandiz, MD, Instituto Nacional de Salúd del Niño, Breña, Peru.
¹¹ V. Gerloni, MD, Istituto Ortopedico Gaetano Pini, Milan, Italy.
¹² P. Quartier, MD, Université de Paris, IMAGINE Institute, RAISE reference centre for rare diseases, Necker-Enfants Malades hospital, AP-HP, Paris, France.
¹³ C.A. Silva, MD, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil.
¹⁴ L. Wagner-Weiner, MD, MS, University of Chicago, Chicago, Illinois, USA.
¹⁵ Y. Gandhi, PhD, R. Wong, MD, Bristol Myers Squibb, Princeton, New Jersey, USA.
¹⁶ J. Passarell, MA, Cognigen Corporation, Buffalo, New York, USA.
¹⁷ M. Nys, MSc, Bristol Myers Squibb, Braine-L'Alleud, Belgium.
¹⁸ A. Martini, MD, IRCCS Istituto G Gaslini, Clinica Pediatrica e Reumatologia, Genoa, Italy and Università di Genova, Genoa, Italy.

PMID: 33452173
DOI: 10.3899/jrheum.200154

Abstract

Objective: To assess the relationship between infection risk and abatacept (ABA) exposure levels in patients with polyarticular-course juvenile idiopathic arthritis (pJIA) following treatment with subcutaneous (SC) and intravenous (IV) ABA.

Methods: Data from 2 published studies (ClinicalTrials.gov: NCT01844518, NCT00095173) of ABA treatment in pediatric patients were analyzed. One study treated patients aged 2-17 years with SC ABA and the other treated patients aged 6-17 years with IV ABA. Association between serum ABA exposure measures and infection was evaluated using Kaplan-Meier plots of probability of first infection vs time on treatment by ABA exposure quartiles and log-rank tests. Number of infections by ABA exposure quartiles was investigated.

Results: Overall, 343 patients were included in this analysis: 219 patients received SC ABA and 124 patients received IV ABA. Overall, 237/343 (69.1%) patients had ≥ 1 infection over 24 months. No significant difference in time to first infection across 4 quartiles of ABA exposure levels was observed in the pooled (P = 0.45), SC (2-5 yrs: P = 0.93; 6-17 yrs: P = 0.48), or IV (P = 0.50) analyses. Concomitant use of methotrexate and glucocorticoids (at baseline and throughout) with ABA did not increase infection risk across the ABA exposure quartiles. There was no evidence of association between number of infections and ABA exposure quartiles. No opportunistic infections related to ABA were reported.

Conclusion: In patients aged 2-17 years with pJIA, no evidence of association between higher levels of exposure to IV ABA or SC ABA and incidence of infection was observed.

Keywords: biological therapy; disease-modifying antirheumatic drugs; infection; juvenile idiopathic arthritis.

Publication types

Clinical Trial, Phase III
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Abatacept* / adverse effects
Antirheumatic Agents* / adverse effects
Arthritis, Juvenile* / drug therapy
Child
Humans
Infections / epidemiology*
Methotrexate / adverse effects
Treatment Outcome

Substances

Antirheumatic Agents
Abatacept
Methotrexate

Associated data

ClinicalTrials.gov/NCT00095173
ClinicalTrials.gov/NCT01844518