Open Access Research article

Double-blind, placebo-controlled randomized trial with adalimumab for treatment of juvenile onset ankylosing spondylitis (JoAS): significant short term improvement

Gerd Horneff1*, Sigrid Fitter1, Ivan Foeldvari2, Kirsten Minden3, Jasmin Kuemmerle-Deschner4, Nicolay Tzaribacev5, Angelika Thon6, Michael Borte7, Gerd Ganser8, Rolf Trauzeddel9 and Hans-Iko Huppertz10

Author affiliations

1 General Pediatrics, Asklepios Clinics, Arnold Janssen Str. 29, Sankt Augustin, 53757, Germany

2 Hamburger Zentrum für Kinder- und Jugendrheumatologie, Klinikum Eilbek, Dehnhaide 120, Hamburg 22081, Germany

3 German Rheumatism Research Centre, Charitéplatz 1, Berlin, 10117, Germany

4 Division of Pediatric Rheumatology, University Hospital Tübingen, Hoppe-Seyler-Straße 1, Tuebingen, 72076, Germany

5 Department für Kinderrheumatologie, Klinikum Bad Bramstedt, Oskar-Alexander-Straße 26, Bad Bramstedt, 24576, Germany

6 Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School Carl-Neuberg-Straße 1, Hannover, 30625, Germany

7 Department for Pediatric Rheumatology, Klinikum St. Georg, Delitzscher Straße 141, Leipzig, 04129, Germany

8 Department of Paediatric Rheumatology, St. Josef-Stift Sendenhorst, Westtor 7 Sendenhors, 48324, Germany

9 4Klinik für Kinder- und Jugendmedizin, Helios Klinikum Berlin-Buch, Schwanebecker Chaussee 50, Berlin, 13125, Germany

10 Department of Pediatrics, Prof. Hess-Kinderklinik, St.-Jürgen-Straße 1, Bremen, 28177, Germany

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Citation and License

Arthritis Research & Therapy 2012, 14:R230  doi:10.1186/ar4072

Published: 24 October 2012

Abstract

Introduction

While adalimumab is licensed for ankylosing spondylitis (AS), open uncontrolled studies suggest therapeutic efficacy of TNF-inhibitors in juvenile onset AS (JoAS).

Methods

A total of 32 patients aged 12 to 17 years with severe, active and refractory JoAS were enrolled in a multicenter, randomized, double-blind, placebo-controlled parallel study of 12 weeks, followed by open-label adalimumab until week 24 for all patients. ASAS40 was used as the primary, and ASAS20, PedACR and single items were used as the secondary outcome measures for the intention to treat population.

Results

A total of 17 patients were randomized to receive adalimumab 40 mg/2 weeks and 15 patients received placebo. Two patients (one of each group) discontinued prematurely due to insufficient efficacy and were labeled as non-responders. In the double-blind part, more patients on adalimumab achieved an ASAS40 at week 4 (41%), week 8 (53%) and week 12 (53%) than on placebo (20%, 33%, 33%), while differences at week 8 only reached borderline significance (P = 0.05). Also, at 4, 8 and 12 weeks ASAS20/PedACR30/70 response rates were higher in the adalimumab group (53%/53%/29%; 59%/76%/41%; 53%/65%/53%) compared to placebo (27%/27%/7%; 27%/33%/13%; 33%/40%/27%). In the adalimumab group a significant decrease of all disease activity parameters was noted at week 12 and was even more pronounced at week 24. At week 12 the Bath Ankylosing Spondylitis Disease activity spinal inflammation score decreased by 65% (P <0.001), the back pain score decreased by 50% (P <0.005), the Bath AS Functional Index (BASFI) score decreased by 47% (P <0.02), while the Childhood Health Assessment Questionnaire-Disability Index (CHAQ-DI) score improved by 65% (P <0.005). ANCOVA analysis demonstrated superiority of adalimumab over placebo for the physician global assessment of disease activity, parents' global assessment of subject's overall well-being, active joint count (all P <0.05) and erythrocyte sedimentation rate (ESR) (P <0.01).

During the 12-week controlled phase, 29 AEs occurred in 10 patients on placebo compared to 27 AEs in 11 patients on adalimumab. Injection site reactions were the most common adverse events. There were 17 various infections occurring in the double-blind phase, 8 on placebo, 9 on adalimumab and a further 19 in the open label period.

Conclusions

Adalimumab was well tolerated and highly effective in a double-blind randomized trial in patients with JoAS. Treatment effects rapidly occurred and persisted for at least 24 weeks of treatment.

Trial registration

EudraCT 2007-003358-27.