LIVERPOOL, ENGLAND – Biologic therapy has shown sustained benefits for the signs and symptoms of juvenile idiopathic arthritis as well as improved height over the course of up to 2 years of treatment, according to data from four studies presented at the British Society for Rheumatology annual conference.
The studies provided evidence indicating that:
• Treatment with etanercept over 2 years helped children with juvenile idiopathic arthritis (JIA) to gain height, although their overall vertical growth still lagged behind children in the general reference population.
• When etanercept was not used as a first-line biologic, it was most common to use adalimumab instead, followed by tocilizumab and infliximab.
• Adalimumab reduced the signs and symptoms of enthesitis-related arthritis (ERA) in children by week 12 of treatment and the effects were sustained at 1-year of follow up.
• The benefits of tocilizumab in reducing disease activity to a minimal level were preserved from 40 weeks to 2 years in most patients.
Etanercept and growth in JIA
"Etanercept therapy was associated with improvement in height z score over the first 2 years of therapy," and the effect was most apparent in children who were not receiving concomitant steroids, said Lianne Kearsley-Fleet, who reported data from the British Society for Paediatric and Adolescent Rheumatology (BSPAR Etanercept Cohort Study). The prospective, observational study was initiated in 2004 with the aim of recruiting all children with JIA who were starting treatment with etanercept. For comparison, a cohort of children newly starting methotrexate was also included.
The current analysis focused on the growth of children taking the biologic therapy because children with JIA are known to have restricted growth, which may be linked to inflammation and the use of corticosteroids. Of 658 children registered in the study, 191 had height data available at baseline and at 1 and 2 years’ follow-up.
Mean height and changes in height during biologic therapy over time were assessed by calculating z scores, and compared with values set by the World Health Organization for girls and boys of a similar age who did not have JIA.
The mean age of children included in the current analysis was 11 years, with a mean disease duration of 3.5 years. The majority (65%) were female, with concomitant oral steroids in 38% and methotrexate in 58%.
The mean height z score of the study population was –0.67 at baseline, –0.57 after 1 year, and –0.45 after 2 years’ etanercept therapy. "While it is still negative [compared with children of a similar sex and age], there is still significant improvement," said Ms. Kearsley-Fleet, a research assistant from the Arthritis Research UK Centre for Epidemiology at the University of Manchester, England.
"There was a lack of evidence for association between disease activity and improved growth," the researcher noted, adding that "anti-TNF inhibitors alone may be insufficient to increase growth."
Use of non–etanercept biologics
In a poster presentation at the meeting, Ms. Kearsley-Fleet and her colleagues at her institution also presented the findings from the Biologics for Children with Rheumatic Diseases Study. This ongoing, prospective, observational cohort study is looking at the use of biologics other than etanercept in the treatment of JIA.
Since the study started in 2010, and up until early April 2014, a total of 280 children with JIA had been recruited into the biologic cohort. The study also includes a parallel control cohort of 295 children being treated with methotrexate. Just under half (46%) of the children recruited into the biologic cohort started a non–etanercept biologic as their first biologic treatment, of which the majority (75%) received the medications off label. The main alternatives to etanercept being used were adalimumab in 38% of cases, followed by tocilizumab in 25% of children, and infliximab in 23%. Other drugs used as the first biologic was anakinra (13%), rituximab (less than 1%), and abatacept (less than 1%).
Adalimumab was also a popular subsequent biologic choice in 30% of cases, with 20% of patients using tocilizumab, and 25% infliximab as a subsequent biologic choice.
The research team reported that patients using a biologic for the first time were significantly younger and had shorter disease durations than did subsequent biologic users. The mean ages of first-, second-, and third-line users were 9, 12, and 11 years, respectively, and the mean disease durations were 2, 6, and 4 years. Subsequent biologic users also had higher active and limited joint counts than did first-time users.
Adalimumab reduces enthesitis-related arthritis symptoms
"Enthesitis-related arthritis is a category of juvenile idiopathic arthritis that primarily affects the peripheral joints and entheses, but can also affect the sacroiliac joints and spine," said Iain Sainsbury, Ph.D., associate director for RA in global medical affairs at AbbVie, in a presentation of data on the efficacy and safety of adalimumab in children with enthesitis-related arthritis (ERA) from the M11-328 study on behalf of the study’s authors.