Dataset Information

Can quantitative MRI be used in the clinical setting to quantify the impact of intra-articular glucocorticoid injection on synovial disease activity in juvenile idiopathic arthritis?

ABSTRACT:

Background

Juvenile idiopathic arthritis (JIA), the most common chronic rheumatic disease of childhood, is characterised by synovitis. Clinical assessments of synovitis are imperfect, relying on composite and indirect measures of disease activity including clinician-reported measures, patient-reported measures and blood markers. Contrast-enhanced MRI is a more sensitive synovitis assessment technique but clinical utility is currently limited by availability and inter-observer variation. Improved quantitative MRI techniques may enable future development of more stringent MRI-defined remission criteria. The objective of this study was to determine the utility and feasibility of quantitative MRI measurement of synovial volume and vascularity in JIA before and twelve weeks after intra-articular glucocorticoid injection (IAGI) of the knee and to assess the acceptability of MRI to participating families.

Methods

Children and young people with JIA and a new episode of knee synovitis requiring IAGI were recruited from the Great North Children's Hospital in Newcastle upon Tyne. Quantitative contrast-enhanced MRI was performed prior to and twelve weeks after IAGI, in addition to standard clinical assessment tools, including the three-variable clinical juvenile arthritis disease activity score (cJADAS) and active joint count.

Results

Eleven young people (5 male, median age 13?years, range 7-16) with JIA knee flare were recruited and 10 completed follow-up assessment. Following IAGI, the median (interquartile range) cJADAS improved from 8.5 (2.7) to 1.6 (3.9), whilst the median synovial volume improved from 38.5cm³ (82.1cm³) to 0.0cm³ (0.2cm³). Six patients presented with frank synovitis outside normal limits on routine MRI reporting. A further three had baseline MRI reports within normal limits but the quantitative measurements identified measurable synovial uptake. Post-IAGI quantitative measurements highlighted significant improvements in 9 patients.

Conclusions

IAGI led to a marked reduction in synovial volume, with quantitative MRI identifying more patients with an improved synovial volume than routine qualitative clinical reporting. Improvements in cJADAS scores were more variable with the patient/parent global assessment component contributing most to the scores. Further work is indicated, exploring the utility of quantitative MRI in the assessment of less accessible joints and comparing the impact of different treatment modalities.

SUBMITTER: Bennett JL

PROVIDER: S-EPMC6873560 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Can quantitative MRI be used in the clinical setting to quantify the impact of intra-articular glucocorticoid injection on synovial disease activity in juvenile idiopathic arthritis?

Bennett Joshua L JL Wood Amanda A Smith Nicola N Mistry Ravi R Allen Karen K Jandial Sharmila S Tuckett John D JD Gowdy S Claire SC Foster Helen E HE McErlane Flora F Hollingsworth Kieren G KG

Pediatric rheumatology online journal 20191121 1

<h4>Background</h4>Juvenile idiopathic arthritis (JIA), the most common chronic rheumatic disease of childhood, is characterised by synovitis. Clinical assessments of synovitis are imperfect, relying on composite and indirect measures of disease activity including clinician-reported measures, patient-reported measures and blood markers. Contrast-enhanced MRI is a more sensitive synovitis assessment technique but clinical utility is currently limited by availability and inter-observer variation. ...[more]

PMID: 31752877

Similar Datasets

Project description:Treatment for idiopathic adhesive capsulitis or frozen shoulder of the shoulder is controversial. The hypothesis of the study is that intra-articular corticosteroid injection in the early stages of idiopathic adhesive capsulitis will lead to a rapid resolution of stiffness and symptoms. This is a retrospective cohort study of only patients with stage 1 or stage 2 adhesive capsulitis. The diagnosis was made by history and physical examination and only when other causes of pain and motion loss were eliminated. Stage 1 adhesive capsulitis was defined as significant improvement in pain and normalization of motion following intra-articular injection. Stage 2 included patients who had significant improvement in pain and partial improvement in motion following injection. Seven patients with stage 1 and 53 patients with stage 2 comprised the baseline cohort. The mean age was 52 years (range: 30 to 78); 46 patients were female and nine patients had diabetes mellitus. Patients completed a physical examination as well as a shoulder rating questionnaire for symptoms and disability. Criteria for resolution were defined as forward flexion and external rotation to within 15 degrees of the contralateral side and internal rotation to within three spinal levels of the contralateral side. Forty-four of the patients out of 60 met the criteria for recovery at a mean of 6.7 months. The mode and median time to recovery was 3 months. The mean score at final follow-up for 41 patients using the shoulder-rating questionnaire of L'Insalata was 90 (range 52-100). The mean time to recovery for the stage 1 patients was 6 weeks (range: 2 weeks to 3 months), and it was 7 months for stage 2 patients (range: 2 weeks to 2 years). Glenohumeral corticosteroid injection for early adhesive capsulitis may have allowed patients to recover motion at a median time of 3 months. In many cases, the patients had improvement prior to the 3-month mark; however, that was the routine time for follow-up. Patients with stage 1 disease tended to resolve more rapidly than stage 2 patients. Prompt recognition of stage 1 and stage 2 idiopathic adhesive capsulitis and early injection of corticosteroid with local anesthesia may be both diagnostic and therapeutic.

Project description:Most forms of arthritis are incurable, difficult to treat, and a major cause of disability in Western countries. Better local treatment of arthritis is impaired by the pharmacokinetics of the joint that make it very difficult to deliver drugs to joints at sustained, therapeutic concentrations. This is especially true of biologic drugs, such as proteins and RNA, many of which show great promise in preclinical studies. Gene transfer provides a strategy for overcoming this limitation. The basic concept is to deliver cDNAs encoding therapeutic products by direct intra-articular injection, leading to sustained, endogenous synthesis of the gene products within the joint. Proof of concept has been achieved for both in vivo and ex vivo gene delivery using a variety of vectors, genes, and cells in several different animal models. There have been a small number of clinical trials for rheumatoid arthritis (RA) and osteoarthritis (OA) using retrovirus vectors for ex vivo gene delivery and adeno-associated virus (AAV) for in vivo delivery. AAV is of particular interest because, unlike other viral vectors, it is able to penetrate deep within articular cartilage and transduce chondrocytes in situ. This property is of particular importance in OA, where changes in chondrocyte metabolism are thought to be fundamental to the pathophysiology of the disease. Authorities in Korea have recently approved the world's first arthritis gene therapy. This targets OA by the injection of allogeneic chondrocytes that have been transduced with a retrovirus carrying transforming growth factor-?1 cDNA. Phase III studies are scheduled to start in the United States soon. Meanwhile, two additional Phase I trials are listed on Clinicaltrials.gov , both using AAV. One targets RA by transferring interferon-?, and the other targets OA by transferring interleukin-1 receptor antagonist. The field is thus gaining momentum and promises to improve the treatment of these common and debilitating diseases.

Project description:ObjectiveTo determine the synovial fluid (SF) concentrations of lidocaine and mepivacaine after intra-articular injection with clinically relevant doses to the distal interphalangeal (DIP), metacarpophalangeal (MCP), middle carpal (MC), and tarsocrural (TC) joint at two different time points after injection in order to be able to compare concentrations with previously established concentrations associated with cytotoxicity and antimicrobial activity.ProceduresIn the first of two experiments, 20 joints (5 MC, 5 MCP, 10 DIP joints) of five horses under general anesthesia were injected with clinically referenced doses of 2% lidocaine. Simultaneously, the horses had 19 joints (5 MC, 5 MCP, 9 DIP joints) injected with clinically referenced doses of 2% mepivacaine. Synovial fluid samples were collected ~7 min after injection. In experiment 2, 23 joints of seven horses under standing sedation were injected with clinically referenced doses of 2% lidocaine. Similarly, the horses had 21 joints injected with 2% mepivacaine. Synovial fluid samples were collected ~23 min after injection. The concentration of mepivacaine and lidocaine in the obtained SF samples was assessed using high-performance-liquid-chromatography with mass spectrometry detection (HPLC MS).ResultsSynovial fluid was obtained 6.8 ± 1.5 (experiment 1) and 23 ± 4.3 (experiment 2) min following intra-articular injection of mepivacaine and lidocaine. Synovial fluid concentrations of experiment 1 for lidocaine and mepivaciane were 6.46-19.62 mg/mL (mean 11.96 ± SD 3.89 mg/mL) and 5.01-13.38 mg/mL (mean 8.18 ± SD 1.76 mg/mL), respectively. In experiment 2, concentrations were 2.94-10.40 mg/mL (mean 6.31± SD 2.23 mg/mL) for lidocaine and 2.10-8.70 mg/mL (mean 4.97 ± SD 1.77 mg/mL) for mepivacaine.Conclusions and clinical relevanceIntra-articular LA injections in horses resulted in SF concentrations above those previously associated with cytotoxic effects in vitro but also above those associated with beneficial antimicrobial activities. Local anesthetic concentration was 33-60% lower after 23 min (experiment 2) than after 7 min (experiment 1).

Project description:BackgroundThe glucocorticoid receptor gene (NR3C1) has been suggested as a candidate gene affecting juvenile idiopathic arthritis (JIA) course and prognosis. The purpose of this study is to investigate the glucocorticoid receptor gene BclI polymorphism (rs41423247) in JIA patients, the gene's role in susceptibility to juvenile idiopathic arthritis, and its associations with JIA activity, course and bone mineralization.MethodsOne hundred twenty-two Caucasian children with JIA and 143 healthy ethnically matched controls were studied. We checked markers of clinical and laboratory activity: morning stiffness, Ritchie Articular Index (RAI), swollen joint count (SJC), tender joint count (TJC), physician's visual analog scale (VAS), hemoglobin level (Hb), leukocyte count (L), platelet count (Pl), Westergren erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), albumin, DAS and DAS28. Bone mineralization was measured by dual-energy X-ray absorptiometry (DXA) of lumbar spine L1-L4. Assessments of bone metabolism included osteocalcin, C-terminal telopeptide (CTT), parathyroid hormone (PTH), total and ionized calcium, inorganic phosphate and total alkaline phosphatase (TAP). BclI polymorphism was genotyped by polymerase chain reaction restriction fragment length polymorphism.ResultsNo association was observed between glucocorticoid receptor gene polymorphism and the presence or absence of JIA. In girls with JIA, the presence of the G allele was associated with an unfavorable arthritis course, a younger age of onset of arthritis (p = 0.0017), and higher inflammatory activity. The higher inflammatory activity was demonstrated by the following: increased time of morning stiffness (p = 0.02), VAS (p = 0.014), RAI (p = 0.048), DAS (p = 0.035), DAS28 (p = 0.05), Pl (p = 0.003), L (p = 0.046), CRP (p = 0.01). In addition, these patients had bone metabolism disturbances as follows: decreased BA (p = 0.0001), BMC (p = 0.00007), BMD (0.005) and Z score (p = 0.002); and higher levels of osteocalcin (p = 0.03), CTT (p = 0.036), TAP activity (p = 0.01) and ionized calcium (p = 0.017). In boys with JIA, no significant differences were observed related to the polymorphic alleles or genotypes.ConclusionsWe suggest that G allele and the GG genotype of the glucocorticoid receptor gene BclI polymorphism contribute to an unfavorable course and low bone mineral density in girls with JIA.

Project description:ImportanceIntra-articular (IA) glucocorticoid injection is widely used in patients with knee osteoarthritis (OA), but the safety of this technique is in question among physicians. Intramuscular (IM) glucocorticoid injection could be an alternative approach.ObjectiveTo investigate whether an IM glucocorticoid injection is noninferior to an IA glucocorticoid injection in reducing knee pain for patients with knee OA in primary care.Design, setting, and participantsThe KIS trial, a multicenter, open-label, randomized clinical noninferiority trial including patients with symptomatic knee OA, was conducted in 80 primary care general practices in the southwest of the Netherlands. The study was conducted from March 1, 2018, to July 28, 2020.InterventionsPatients were randomly allocated to receive an injection of triamcinolone acetonide, 40 mg, either IM in the ipsilateral ventrogluteal region or IA in the knee joint. All patients were followed up for 24 weeks.Main outcomes and measuresThe pain score at 4 weeks measured with Knee Injury and Osteoarthritis Outcome Score (range, 0-100; 0 indicates extreme pain), with a noninferiority margin of -7 (IM minus IA). A per-protocol analysis was prespecified as the primary analysis.ResultsA total of 145 patients (94 women [65%]; mean [SD] age, 67 [10] years) were included; of these, 138 patients (IM, 72; IA, 66) were included in the per-protocol analysis. Clinically relevant improvements in knee pain were reached up to 12 weeks after the injection in both groups. At 4 weeks, the estimated mean difference in the Knee Injury and Osteoarthritis Outcome Score between the 2 groups was -3.4 (95% CI, -10.1 to 3.3). Noninferiority could not be declared because the lower limit exceeded the noninferiority margin. Intramuscular injection was noninferior to IA injection at 8 (mean difference, 0.7; 95% CI, -6.5 to 7.8) and 24 (mean difference, 1.6; 95% CI, -5.7 to 9.0) weeks. No significant difference was found among all the secondary outcomes. These results were similar for the sensitivity analysis in an intention-to-treat population. The most frequently reported adverse events were hot flush (IM, 7 [10%] vs IA, 14 [21%]) and headache (IM, 10 [14%] vs IA, 12 [18%]), and all events were classified as nonserious.Conclusions and relevanceBased on the findings of this trial, among patients with knee OA in primary care, IM glucocorticoid injection could present an inferior effect in reducing pain at 4 weeks compared with IA injection. Noninferiority of an IM injection was observed at 8 and 24 weeks after injection. This trial provides data for shared decision-making, taking into account the advantages and disadvantages of both types of injections.Trial registrationDutch Trial Registry: NTR6968.

Project description:BackgroundJuvenile Idiopathic Arthritis (JIA) commonly affects joints of the lower limb including the knee, ankle, subtalar and other foot joints. Intra-articular corticosteroid injections (IACIs) are considered to be effective for short-term relief of synovitis, however, there appears to be a significant lack of published evidence from comparative effectiveness studies. The aim of this study was to identify and critically appraise the evidence for the efficacy of lower limb IACIs in children/adolescents with JIA.MethodsStudies were identified in databases Medline, Embase, CINAHL, AMED, PEDro, the Cochrane Library and TRIP, with no date restrictions. The primary search terms 'juvenile idiopathic arthritis', 'lower limb', 'knee'; 'ankle', 'foot' and 'intra-articular steroid injections' and related synonyms were used to develop a comprehensive pragmatic literature search strategy. Included studies were quantitative longitudinal design such as randomised controlled trials, pseudo-randomised and non-randomised experimental studies, cohort studies, and case-control studies. All outcomes measures were subject to analysis. Quality assessment was conducted using the Cochrane Collaboration criteria with additional criteria for sample population representativeness, quality of statistical analysis and compliant intervention use and presence of co-interventions. Qualitative data synthesis was conducted for the outcome domains. Meta-analyses were not possible as multiple randomised controlled trials for outcome measures were not available. Levels of evidence were assigned to each outcome measure.ResultsThe inclusion criteria were met by twenty-one studies. One study had high quality for internal validity and nine studies had high quality for external validity. No studies had high quality for both internal and external validity. Four outcome domains were identified. There was weak evidence for IACIs decreasing clinical signs and symptoms in the lower leg, improving joint range of motion, decreasing leg length discrepancy, and for imaging techniques detecting the effects of IACIs.ConclusionsThere is some weak evidence for the efficacy of IACIs improving certain outcome measures. However, there is also some inconclusive evidence due to a lack of quality studies. More high quality evidence is necessary to definitely determine the efficacy of IACIs for JIA in the lower leg.

Dataset Information

Can quantitative MRI be used in the clinical setting to quantify the impact of intra-articular glucocorticoid injection on synovial disease activity in juvenile idiopathic arthritis?

Background

Methods

Results

Conclusions

Publications

Can quantitative MRI be used in the clinical setting to quantify the impact of intra-articular glucocorticoid injection on synovial disease activity in juvenile idiopathic arthritis?

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets