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Clinical Trial Design in Juvenile Idiopathic Arthritis.

ABSTRACT: Randomized clinical trials provide the gold standard evidence base to guide clinical practice. Despite major advances in trial design, pediatric clinical trials are still difficult to perform and pose unique challenges, including the need to consider the impact of developmental changes in trial design. Advances within pediatric rheumatology combined with the need to comply with legislative requirements have driven new approaches to performing pediatric clinical trials such as utilization of large research networks, incorporation of patient and family stakeholders in the planning and implementation of clinical trials, and the development of novel trial designs. The expansion of available biological therapeutics that now includes biosimilar drugs highlights the important and difficult balance of providing new and cost-effective drugs to children while ensuring safety in a vulnerable population. Future advances in juvenile idiopathic arthritis (JIA) clinical trials will likely be the application of precision medicine based on biologic, rather than phenotypic, classification of JIA, with improved understanding of pediatric clinical pharmacology. Clinical trial simulations and comparative effectiveness studies are important supplements to traditional clinical trials, permitting efficient studies and results that are more generalizable.

SUBMITTER: Balevic SJ

PROVIDER: S-EPMC6105333 | biostudies-other | 2017 Oct

REPOSITORIES: biostudies-other

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Clinical Trial Design in Juvenile Idiopathic Arthritis.

Balevic Stephen J SJ Becker Mara L ML Cohen-Wolkowiez Michael M Schanberg Laura E LE

Paediatric drugs 20171001 5

Randomized clinical trials provide the gold standard evidence base to guide clinical practice. Despite major advances in trial design, pediatric clinical trials are still difficult to perform and pose unique challenges, including the need to consider the impact of developmental changes in trial design. Advances within pediatric rheumatology combined with the need to comply with legislative requirements have driven new approaches to performing pediatric clinical trials such as utilization of larg ...[more]

PMID: 28612093

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Project description:ObjectivesThis study aimed at evaluating the effect of genicular nerve block (GNB) in juvenile idiopathic arthritis (JIA) patients with persistent unilateral knee arthritis on pain, inflammatory parameters, function, and range of motion.MethodsA total of 104 JIA patients were diagnosed according to the International League Against Rheumatism (ILAR) criteria with persistent unilateral knee arthritis. They were allocated randomly into 2 groups: group 1 treated with GNB, while group 2 was treated with intra-articular triamcinolone (TA) only. Visual analogue scale (VAS) on pain, sonography of large joints in rheumatology (SOLAR) scoring system, and Lysholm scores were assessed at 0-, 2-, and 12-week intervals. Swelling and tenderness were clinically evaluated semi-quantitatively (0-3) at the same time intervals.ResultsVAS pain, tenderness, swelling, and SOLAR grey scale (GS) and power Doppler (PD) scores were significantly reduced after 2 weeks in both groups (p < 0.05). This was greater in the GNB group regarding VAS and tenderness, while SOLAR and swelling were stronger reduced in TA group. After 12 weeks, all outcome measures showed lower values in the GNB group compared to TA, and this was significant regarding VAS pain. Moreover, Lysholm functional score was significantly increased in both groups at both intervals; and higher values were seen in the TA group compared to GNB after 2 weeks.ConclusionGNB was able to control pain and improve function and inflammation of the knee joint in JIA patients. Though steroid attained better results after 2 weeks, GNB achieved an equivalent longer-term improvement after 12 weeks.Trial registration identifying numberNCT04687930. Key Points • Persistent knee arthritis treatment in JIA is always challenging. • GNB was approved for treatment of pain in knee osteoarthritis. • GNB in the present study succeeded to control active knee arthritis and this effect was comparable to intra-articular steroid injection.

Project description:BackgroundHaptoglobin (Hp), a liver derived acute phase inflammatory protein (APP), has scarcely been studied in juvenile idiopathic arthritis (JIA). Hp can occur in blood as two isoforms (Hp1 and Hp2) in precursor and mature forms. Routine clinical chemistry immunoturbidimetry does not discern these forms. It is unknown how different forms relate to disease activity in JIA. Our aims were to determine allele frequency and plasma concentrations of different Hp forms at higher versus lower JIA disease activity and compare to other APPs.MethodsPlasma from JIA (n = 77) and healthy (n = 42) children were analyzed for apparent Hp allelic frequency and densitometric concentrations of alpha forms by Western blot (WB). Polymerase chain reaction (PCR) (buffy coat) was performed in a subset to estimate conformity with genetics. At higher versus lower juvenile arthritis disease activity score (JADAS27) (which includes erythrocyte sedimentation rate (ESR)), total mature Hp concentration from WB was compared and correlated against immunoturbidimetry and total protein, albumin, serum amyloid A (SAA) and C-reactive protein (CRP).ResultsAt 300-fold dilution needed to study mature forms in Western blot, precursors were undetectable. Hp2 contributed most signal in most samples. Hp allele frequency was similar in JIA and controls. Both mature forms, taken separately or by sum, declined following treatment, but remained above concentrations of healthy controls, even in a remission subset that achieved JADAS27 < 1. Densitometry correlated with immunoturbidimetry. Hp concentrations correlated with JADAS27, albumin (negatively), CRP and SAA with immunoturbidimetric method correlating strongest to JADAS27 (Spearman R ~ 0.6, p < 0.0001).ConclusionHp allele frequency in JIA is similar to the general population, indicating that children with JIA should have the same possibility as in healthy children to produce preHp2 (zonulin), thought to increase intestinal permeability. Circulating Hp concentrations largely parallel other APPs and ESR; none of these measures correlate very strongly to JADAS27 score but Hp can be measured from capillary sampling which is impossible with ESR.

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Clinical Trial Design in Juvenile Idiopathic Arthritis.

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Clinical Trial Design in Juvenile Idiopathic Arthritis.

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