June 12, 2009 Three new studies have individually shown the anti-TNF (tumour necrosis factor) therapy etanercept to be effective, with a good safety profile, in children under four years of age with juvenile idiopathic arthritis (JIA), and associated with improved Health-Related Quality of Life (HRQoL) in a substantial proportion of children with JIA. The data are being presented at the Paediatric Rheumatology European Society Congress (PReS) 2009, a joint congress with the 2009 Congress of the European League Against Rheumatism (EULAR) in Copenhagen, Denmark.
The first study, conducted in Italy, showed entanercept to be effective, with a good safety profile, in children under four years of age (an as yet unlicensed patient population for the treatment). Thirty-three patients under four years of age with unresponsive JIA (24 female, 9 male) were treated with etanercept for an average of 23 months. After the first 6 months of treatment, 82% achieved the ACR Pedi 30* response and 48% achieved the ACR Pedi 70* response. There was a low rate of mild adverse events, whilst one patient temporarily suspended treatment following hospitalisation for an infection.
The second study, conducted in The Netherlands, from the Arthritis and Biological in Children (ABC) project, observed impressive improvements in the Health-Related Quality of Life (HRQoL) of 53 patients with previously refractory (unresponsive) JIA in seven Dutch centres during entanercept use of at least 27 months. These comprised both disease-specific improvements (inflamed joints, functional impairment, erythrocyte sedimentation rate (ESR), a laboratory marker of inflammation) (p<0.001) and all generic HRQoL outcomes impaired by JIA (including pain, movement and dexterity) (p<0.05).
The third study, also from The Netherlands ABC-project, showed that a substantial 57% of non-responders to etanercept at three months (12 patients from 21 non-responders of a total of 179 JIA patients; average age of 5.8 years) who continued with the treatment eventually responded. The researchers in this study thereby suggest extending the use of etanercept in non-responding patients beyond the commonly recommended three-month therapy window to achieve higher response rates in JIA patients.
* The American College of Rheumatology (ACR) pediatric criteria assess patient response to a treatment. An ACR Pedi 30 response represents a >30% improvement in JIA signs and symptoms, such as the number of swollen joints with loss of motion, assessment of pain and level of disability. ACR Pedi 50 represents a >50% improvement, and ACR Pedi 70 represents a >70% improvement.
Further details on the three studies are outlined below:
1. Safety and efficacy of etanercept in a cohort of juvenile idiopathic arthritis (JIA) patients under four years of age. (OP-0137)
Thirty-three patients with unresponsive JIA under four years of age in a single centre were treated with etanercept for a mean of 23 months (range 6-86), with all receiving other concurrent drug treatments. Efficacy (using ACR Pediatric 30, 50 and 70 criteria for improvement) and safety end points were recorded at each hospital visit.
The ACR Pedi 30 response was reached by 82% (27) after 6 months and 85% (28) at the last observation. The ACR Pedi 50 response was reached by 76% (25) at 6 months and 85% (28) at the last follow-up, and the ACR Pedi 70 response was reached by 48% and 73% respectively.
Four patients (12%) developed mild adverse events: including one case of cytomegalovirus infection and three varicella zoster virus (VZV) infections. One patient experienced a serious adverse event and was hospitalised for a necrotising fasciitis during VZV infection. No cases of tuberculosis, opportunistic infections or malignancies were reported.
2. Major improvements in health-related quality of life during the use of etanercept in patients with refractory juvenile idiopathic arthritis. (THU0426)
In 53 JIA patients, who previously did not respond to other second-line drugs, data were collected to evaluate HRQoL during treatment with etanercept. HRQoL was measured by the Childhood Health Assessment Questionnaire (CHAQ), Child Health Questionnaire (CHQ) and Health Utilities Index mark 3 (HUI3) before start and after 3, 15 and 27 months. At the same time-points, information on JIA disease activity variables were also collected, including; physician's global assessment through the Visual Analogue Scale (VAS), number of active and limited joints and erythrocyte sedimentation rate. Linear mixed models were used to assess outcomes over time.
Significant improvements in HRQoL were seen during the 27 month study period. The disease specific CHAQ, including the VAS pain and VAS well-being scores showed a significant improvement on all domains (p<0.001). The generic health-profile measure CHQ improved on all the health concepts (p<0.05) except 'family cohesion', which is known to be unaffected by JIA.1 The generic preference-based HUI3 showed significant improvement (p<0.05) on the more specific areas of 'pain', 'ambulatory', and 'dexterity'. In accordance, disease activity variables improved significantly over time (p<0.001).
Dr Femke H.M. Prince of the Erasmus MC Sophia Children's Hospital, Rotterdam, The Netherlands, said: "JIA, the most common cause of chronic arthritis in children, frequently results in physical disabilities and chronic pain influencing daily life. The results for the Arthritis and Biologicals in Children project show impressive improvement on all domains of Health-Related Quality of Life impaired by JIA during treatment with etanercept. This indicates that these previously severely ill children, as well as their families, gain great benefits from this treatment. The results of our studies add to the bank of research on the role of etanercept in treating JIA patients of all subtypes who previously have not responded to other second-line drugs."
3. Delayed clinical response in patients with juvenile idiopathic arthritis treated with etanercept. (FRI0478)
From 179 JIA patients in the ABC-register, with a minimal follow-up of 15 months, the clinical response was assessed using the American College of Rheumatology Paediatric 30 variables. Of the 34 patients who initially failed to meet these response criteria, 21 continued etanercept therapy and 12 patients reached a delayed response at 15 months of treatment. Overall, 7% of the 179 patients were delayed responders after 3 months of treatment and this was most likely in those with the oligoarticular, arthritis psoriatica and enthesitis related arthritis subtypes.
Dr Marieke H. Otten of the Erasmus MC Sophia Children's Hospital, Rotterdam, The Netherlands, said: 'Biological agents are one of the last therapeutic options for JIA and have shown to be highly effective in refractory patients. Previous studies on etanercept have shown rapid improvements, but the optimal duration to evaluate effectiveness is still unknown. This study shows a delayed clinical response in a substantial proportion of the patients treated with etanercept. We advise, especially in patients with a partial response, to continue treatment to at least six months.'
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