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

ABSTRACT: While adalimumab is licensed for ankylosing spondylitis (AS), open uncontrolled studies suggest therapeutic efficacy of TNF-inhibitors in juvenile onset AS (JoAS).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.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).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.EudraCT 2007-003358-27.

SUBMITTER: Horneff G

PROVIDER: S-EPMC3580542 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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

Horneff Gerd G Fitter Sigrid S Foeldvari Ivan I Minden Kirsten K Kuemmerle-Deschner Jasmin J Tzaribacev Nicolay N Thon Angelika A Borte Michael M Ganser Gerd G Trauzeddel Rolf R Huppertz Hans-Iko HI

Arthritis research & therapy 20121024 5

<h4>Introduction</h4>While adalimumab is licensed for ankylosing spondylitis (AS), open uncontrolled studies suggest therapeutic efficacy of TNF-inhibitors in juvenile onset AS (JoAS).<h4>Methods</h4>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, Pe ...[more]

PMID: 23095307

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Project description:OBJECTIVE:The aim of this study was to evaluate the efficacy and safety of the biosimilar candidate of adalimumab (HS016) compared with adalimumab (Humira) for the treatment of active ankylosing spondylitis. METHODS:A multicenter, randomized, double-blind, parallel, positive control, phase III clinical trial was conducted at 28 locations in China. Patients with active ankylosing spondylitis were randomized in a 2:1 ratio to subcutaneously receive 40 mg of either HS016 or adalimumab every other week for 24 weeks. The primary endpoint was to achieve at least a 20% improvement (ASAS20) in patients at 24 weeks according to the Assessment of Spondyloarthritis International Society criteria. The secondary endpoint included other efficacy assessment parameters, health evaluations, safety, pharmacokinetic, and immunogenicity parameters. RESULTS:Following the random assignment of 648 patients into HS016 (n?=?416) and adalimumab (n?=?232) groups, no significant difference was found in the ASAS20 response rates at 24 weeks between the HS016 (364/416, 87.5%) and adalimumab (209/232, 90.1%) treatments and the difference between the response rates (-?2.59%; 90% confidence interval [CI] -?6.77 to 1.60) was within the predefined equivalence margin (±?15%). There were also no significant differences when the secondary endpoints were compared (all p?>?0.05). Similarly, the rates of treatment-emergent adverse events (TEAEs) were not significantly different between the two groups, with most TEAEs being mild to moderate. Only nine severe cases were found, including seven within the HS016 group, three (0.7%) of which were tuberculosis cases. Plasma concentrations of HS016 and adalimumab from weeks 12 to 14 were similar during the steady-state period and steady-state maximal concentration (Cmax,ss) was equivalent for HS016 (7356.6 ng/mL) and adalimumab (7600.3 ng/mL). The accumulated proportion of patients with positive human anti-human antibodies (HAHAs) at week 24 was 326/412 (79.1%) in the HS016 group and 183/229 (79.9%) in the adalimumab group (p?>?0.05), while the accumulated proportion of patients with positive neutralizing antibody (NAb) tests were 72/412 (17.5%) in the HS016 group and 43/229 (18.8%) in the adalimumab group (p?>?0.05). CONCLUSION:HS016 resembled adalimumab in efficacy and safety over the 24-week treatment period. TRIAL REGISTRATION NUMBER:ChiCTR1900022520.

Dataset Information

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

Publications

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

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