The German Etanercept Registry for Treatment of Juvenile Idiopathic Arthritis (JIA)

Gerd Horneff ^1*, Heinrike Schmeling ², Thomas Biedermann ³, Ivan Foeldvari ⁴, Gerd Ganser ⁵, Hermann J Girschick ⁶, Thomas Hosbach ⁷, H Iko Huppertz ⁸, Rolf Keitzer ⁹, R M Kuester ¹⁰, Hartmut Michels ¹¹, Dagmar Moebius ¹², Bettina Rogalski ¹³ and Angelika Thon ¹⁴

¹ University of Halle, Germany
² University Medical Centre, Martin-Luther-University, Halle-Wittenberg, Germany
³ HELIOS Klinikum, Berlin, Germany
⁴ AK Eilbeck, Germany
⁵ North-West-Germany Centre of Rheumatology, St. Josef Stift, Germany
⁶ University Medical Centre, Würzburg, Germany
⁷ Olga's Children's Hospital, Stuttgart, Germany
⁸ Prof.- Hess-Paediatric Clinic, Bremen, Germany
⁹ Charité, Berlin, Germany
¹⁰ Children's Rheumatology Clinic, Bad-Bramstedt, Germany
¹¹ Children's Rheumatology Clinic, Garmisch-Partenkirchen, Germany
¹² Carl-Thiem Hospital, Cottbus, Germany
¹³ Children's Rheumatology Clinic Neckargemünd, Germany
¹⁴ University Medical Centre, Hannover, Germany

^* To whom correspondence should be addressed. E-mail: gerd.horneff{at}medizin.uni-halle.de.

Accepted 21 March 2004

Abstract

Background: Etanercept has been approved for refractory polyarticular JIA following a randomised controlled study involving 69 patients. Long term data in a larger cohort of children are missing.

Objective: To evaluate long-term feasibility, safety and efficacy, a registry was set up to prospectively monitor children treated with etanercept in Germany and Austria.

Methods: Giannini's criteria, the duration of morning stiffness, the number of swollen, tender and contracted joints, adverse events and reasons for discontinuation were assessed.

Results: So far 322 patients with JIA were included and 12 additional patients with non-JIA rheumatic diagnoses were followed for safety evaluation. Therapeutic efficacy was noted 1 month after therapy was started. The number of patients with significant improvement as well as the strength of improvement further increased during the first year of treatment. The mean+/- SD of morning stiffness decreased from 45+/- 65 min to 12+/-30 and 7+/-19 after 1 and 3 months, respectively, and remained low thereafter (p<0.001 for all points in time). The mean+/- SD of the number of tender and swollen joints decreased from 9+/-9 and 8.4+/- 9 to 3.0+/-6.5 and 4.5+/-7 respectively after 1 month and 2.2+/-5.5 and 3.3+/-5.5 after 3 months and remained low thereafter. According to Gianinni's criteria of 30%, 50% and 70%, a therapeutic response was achieved with 66%, 54% and 30% after 1 month, 78%, 61% and 38% at 3 months and 83%, 72% and 52% of JIA patients after 6 months of therapy, and remained stable thereafter. Subtype analysis revealed a marked lower therapeutic efficacy in patients with systemic onset arthritis. At 6 months of therapy 56% of these did reach the 30% response criteria, 44% the 50% criteria, in contrast to 88% of non-systemic JIA patients who met the 30% and 78% the 50% efficacy level. Overall tolerability was good. In 592 patient treatment years there were 69 reports on adverse events in 56 patients including one CNS demyelinisation. There were no opportunistic infections or lupus-like reactions. 53 JIA patients discontinued therapy; 25 because of lack of efficacy. 14 of them were diagnosed with systemic arthritis. Treatment as discontinued in 12 patients after long-term remission was achieved. In 16 patients the drug was discontinued for other reasons.

Conclusion: Etanercept treatment was safe and led to a significant improvement in the vast majority of JIA-patients resistant to conventional treatment.

Keywords: etanercept, juvenile idiopathic arthritis, tumour necrosis factor

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