Double-blind, placebo-controlled randomized trial with adalimumab for treatment of juvenile onset ankylosing spondylitis JoAS: significant short term improvementReport as inadecuate




Double-blind, placebo-controlled randomized trial with adalimumab for treatment of juvenile onset ankylosing spondylitis JoAS: significant short term improvement - Download this document for free, or read online. Document in PDF available to download.

Arthritis Research and Therapy

, 14:R230

First Online: 24 October 2012Received: 29 April 2012Revised: 17 September 2012Accepted: 18 October 2012

Abstract

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

MethodsA 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.

ResultsA 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.

ConclusionsAdalimumab 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 registrationEudraCT 2007-003358-27.

AbbreviationsADAAdalimumab

AEAdverse event

ANCOVAanalysis of covariance

ASankylosing spondylitis

ASASAssessment of SpondyloArthritis international Society

BASDAIBath Ankylosing Spondylitis Disease activity score

BASFIBath Ankylosing Spondylitis Functional Index

CHAQ-DIChildhood Health Assessment Questionnaire-Disability Index

CRPC-Reactive Protein

DMARDDisease modifying drug

ESRerythrocyte sedimentation rate

FDAFood and Drug Administration

ICH GCPInternational Conference on Harmonisation Good Clinical Practice

ITTintention-to-treat

JIAjuvenile idiopathic arthritis

JoASjuvenile onset ankylosing spondylitis

LOMlimitation of motion

MRIMagnet resonance imaging

NRSnumeric rating scale

NSAIDNonsteroidal anti-inflammatory drug

PedACR criteriapediatric version of the American Colleague or rheumatology criteria

PLCPlacebo

SAESerious adverse event

TNFtumor necrosis factor

Electronic supplementary materialThe online version of this article doi:10.1186-ar4072 contains supplementary material, which is available to authorized users.

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Author: Gerd Horneff - Sigrid Fitter - Ivan Foeldvari - Kirsten Minden - Jasmin Kuemmerle-Deschner - Nicolay Tzaribacev - Angelika 

Source: https://link.springer.com/







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