PubMed Health⌕ Search

Biomedical subjects

Philip G Conaghan

Publications and source records attributed to Philip G Conaghan.

At least 19 recordsLinked to original sources
PubMed2026

Systemic biomarkers of treatment response to methotrexate in people with painful knee osteoarthritis: A biological substudy of the PROMOTE randomised controlled clinical trial.

OBJECTIVE: Stratification of therapeutic responses may help identify efficacious therapies for osteoarthritis (OA). In the PROMOTE randomised trial, participants with elevated baseline high-sensitivity C-reactive protein (hs-CRP) showed greater pain reduction after methotrexate treatment. We set out to interrogate a broader panel of serum/plasma inflammatory response markers relevant to methotrexate actions as potential biomarkers of therapeutic effect. Our objectives were to: (i) characterize changes in these systemic markers during methotrexate treatment; determine whether (ii) baseline levels or (iii) changes in any marker during treatment were associated with treatment response; and (iv) compare these findings with the more established clinical inflammatory marker, hs-CRP. DESIGN: Plasma/serum samples from participants in PROMOTE's biological substudy were analysed for 35 inflammatory markers at baseline (pre-treatment) and at 6-months (post-treatment), by MesoScale V-plex multiplex assay. Those with paired biological and clinical data at both baseline and 6-months were included in the substudy analysis set. Relationships between markers and overall data structure were assessed by Pearson correlation and Principal Component analysis. Associations between markers (baseline levels or change over time) and change in average knee pain severity in past week (numerical rating scale, NRS) were evaluated by univariable linear regression, adjusting for baseline age, sex, and body mass index. Least Absolute Shrinkage and Selection Operator (LASSO) regression with bootstrap resampling enabled marker selection. Benjamini-Hochberg correction adjusted for multiple testing (Padj). RESULTS: 87 participants with paired blood marker and clinical data were eligible for substudy analysis. 18/35 markers were quantifiable and analysed. Systemic IL-8 and TNF-α levels decreased (Padj=0.015, 0.048 respectively) while IL-15 increased (Padj=0.033) with methotrexate treatment over 6-months. Analysing within this active treatment randomised arm, higher baseline IFN-γ was associated with greater reduction in NRS pain change (0.66 [0.01, 1.31], P=0.047), as was decreasing TNF-α over 6-months (2.25 [0.00, 4.5], P=0.049). LASSO identified higher IFN-γ, lower plasma IL-15 and IL-16, and younger age as the most important baseline predictors of pain improvement. hs-CRP was highly selected by LASSO for treatment response in both arms. In a secondary univariate treatment arm-by-biomarker interaction analysis, of the 19 markers, only hs-CRP showed consistent effects in adjusted models (at baseline, coeffic. 2.34 [0.53, 4.15], P=0.001; change over 6-months, (0.36 [0.06, 0.66], P=0.018). CONCLUSIONS: Blood measurement of IFN-γ, TNF-α, IL-15 and IL-16 as well as hs-CRP could act as potential markers to stratify the treatment response by average knee pain to methotrexate in knee osteoarthritis.

Humans↗
PubMed2007

The Foot Posture Index: Rasch analysis of a novel, foot-specific outcome measure.

OBJECTIVE: To investigate the internal construct validity of a clinician-assessed measure of foot position, the Foot Posture Index (FPI), versions FPI-8 and FPI-6. DESIGN: Rasch analysis of baseline FPI scores from studies conducted during the development of the instrument. SETTING: A community-based and a hospital-based study, conducted at 2 institutions. PARTICIPANTS: Measures were obtained from 143 participants (98 men, 45 women; age range, 8-65y). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Rasch analysis was undertaken using RUMM2020 software in order to evaluate the following properties of the FPI: unidimensionality of each item included in the FPI, the differential item functioning (DIF) of each item, and item and person separation indices. RESULTS: In the developmental draft of the instrument, the 8-item FPI-8 showed some misfit to the Rasch model (chi(16)(2) test=27.63, P=.03), indicating lack of unidimensionality. Two items were identified as problematic in the Rasch modeling: Achilles' tendon insertion (Helbing's sign), which showed illogical response ordering and "congruence of the lateral border of the foot," which showed misfit, indicating that this item may be measuring a different construct (chi(2)(2) test=15.35, P<.01). All FPI-8 items showed an absence of DIF, and the person separation index (PSI) was good (PSI=.88). The revised FPI-6, which does not include the 2 problematic items, showed unidimensionality (chi(12)(2) test=11.49, P=.49), indicating a good overall fit to the model, and improvement over the preliminary version. With the removal of the 2 problematic items, there were no disordered thresholds; all items remained DIF free and all individual items displayed a good fit to the model. The person-separation index for the FPI was similar for both the 8-item (FPI-8=.880) and 6-item (FPI-6=.884) versions. CONCLUSIONS: The original FPI-8 showed significant mismatching to the model. The 2 items in the FPI-8 that were identified as problematic in clinical validation studies were also found to be contributing to the lack of fit to the Rasch model. The finalized 6-item instrument showed good metric properties, including good individual item fit and good overall fit to the model, along with a lack of differential item functioning. This analysis provides further evidence for the validity of the FPI-6 as a clinical instrument for use in screening studies and shows that it has the potential to be analyzed using parametric strategies.

Adolescent↗
PubMed2006

Efficacy of infliximab on MRI-determined bone oedema in psoriatic arthritis.

BACKGROUND: Psoriatic arthritis (PsA) is commonly associated with bone pathology, including entheseal new bone formation and osteolysis. On MRI, areas of active clinical involvement are represented by bone oedema and synovitis. AIM: To assess the impact of infliximab on bone oedema in PsA as shown by MRI. METHODS: 18 patients with joint swelling, psoriasis and seronegativity for rheumatoid factor received four infusions of infliximab, 3 mg/kg, in combination with methotrexate. MRI of the affected hand (12 patients) or knee joints (6 patients) was performed before and after treatment. The primary outcome was the assessment of bone oedema and synovitis at 20 weeks as shown by MRI. Secondary outcomes included the American College of Rheumatology (ACR) response criteria, psoriasis skin scores (Psoriasis Area and Severity Index (PASI)) and a quality of life measure (Psoriatic Arthritis Quality of Life (PsAQoL)). RESULTS: At baseline, bone oedema was seen in 50% of patients (seven hands and two knees) in 30% of scanned joints, and this improved or resolved in all cases in the hand joints (p = 0.018) and in one knee joint at 20 weeks. Synovitis was found to be reduced in 90% of cases on MRI. Likewise, a significant improvement in all clinical outcomes, including PASI (p = 0.003) and PsAQoL (p = 0.006) was seen at week 20. 65% (n = 11) of the patients achieved an ACR response, of whom 45% had ACR70 or above and 54% had ACR20 or ACR50. CONCLUSIONS: Infliximab treatment is associated with dramatic improvements in MRI-determined bone oedema in PsA in the short term. It remains to be determined whether infliiximib treatment is the cause for prevention of new bone formation, bone fusion or osteolysis in PsA as shown by radiography.

Adult↗
PubMed2006

Response to intramuscular methyl prednisolone in inflammatory hand pain: evidence for a targeted clinical, ultrasonographic and therapeutic approach.

BACKGROUND: Hand pain with stiffness is a common clinical presentation to early arthritis clinics, with outcome varying from resolution to the development of rheumatoid arthritis. OBJECTIVE: To assess the response and predictors of response to intramuscular methylprednisolone (MP) and hydroxychloroquine (HCQ) using a standardised treatment protocol. METHODS: Patients with inflammatory hand pain (IHP), defined as predominantly hand pain and morning stiffness of at least 30 min duration, received a standardised assessment prior to receiving intramuscular MP. Response (primary outcome) at 4 weeks was a 50% improvement in symptoms as perceived by the patient; responders who relapsed received repeat intramuscular MP and HCQ. RESULTS: 102 patients were recruited, of which 21% were rheumatoid factor (RF) positive, 23% had clinical synovitis, 25% had raised C-reactive protein level and 55% had ultrasound-detected synovitis. 73% responded, with associated significant reductions in morning stiffness, Health Assessment Questionnaire, painful and tender joint counts, and visual analogue scores (p < or = 0.006 for all). Ultrasound-detected synovitis (p<0.001) and RF (p = 0.04), but not clinical synovitis (p = 0.74), were significantly associated with response to intramuscular MP. 86% who remained on HCQ long term reported a benefit. CONCLUSIONS: Patients with IHP have significant improvement in symptoms and function following intramuscular MP. Further placebo-controlled trials are required to assess the role of intramuscular MP and ultrasonography in managing this patient group.

Adult↗
PubMed2006

Impact of multiple joint problems on daily living tasks in people in the community over age fifty-five.

OBJECTIVE: To establish the prevalence of multiple joint problems and their impact on everyday tasks. METHODS: A random sample of the UK population was assessed using a postal questionnaire. Data on overall joint pain, swelling and stiffness, and activities of daily living were obtained from 16,222 individuals >55 years of age (86% response rate). Prevalence estimates of joint problems were established and the impact of multiple joint pathologies on common physical tasks was determined. RESULTS: Single joint involvement was unusual (median joint involvement 4). Although the knee was the most frequently involved joint (220.30 per 1,000), isolated knee pathology accounted for only 1 in 11 patients with knee pain. Although single joint disorders increased the risk of experiencing functional difficulty, this risk was substantially increased with multiple joint problems: individuals with knee and feet problems were 14 times more likely to experience difficulty standing and walking than those without knee problems (odds ratio [OR] 14.50); knee and hip problems increased the risk >12 times (OR 12.43) whereas knee, back, feet, and hip involvement increased the risk 60 times (OR 62.41). CONCLUSION: Multiple-site joint problems are much more common than single joint problems. Although individual joint problems have a considerable impact on a person's functional ability, this risk is substantially increased when other joints are involved. With the increasing burden associated with the aging population, it is essential that the management of joint pain be considered in light of the impact of multiple, rather than single, joint problems.

Activities of Daily Living↗
PubMed2006

Quantifying peri-meniscal synovitis and its relationship to meniscal pathology in osteoarthritis of the knee.

The objectives of this study were to validate a semiquantitative scoring system for estimating perimeniscal synovitis in osteoarthritic (OA) knees and to examine the relationship between the extent of synovitis and the degree of meniscal pathology using gadolinium-enhanced magnetic resonance imaging (MRI). Forty-three subjects with clinically diagnosed OA knee were assessed for peri-meniscal synovitis using gadolinium-enhanced MRI. Quantitative measurements of synovitis were made by summing areas in consecutive slices within generated regions of interest, and the synovitis was also scored semi-quantitatively using a 0-3 scale. Meniscal pathology (extrusion, degeneration and tearing) was also scored semiquantitatively. Establishment of a correlative relationship was undertaken using Spearman's rho (rho). A total of 86 sites were assessed. The semi-quantitative synovitis score correlated well with the quantitative synovitis score (rho>0.9). A moderate association between medial meniscal extrusion and synovitis was demonstrated (rho=0.762, P<0.000), although this association was not as strong in the lateral compartment (rho=0.524, P<0..000). The results suggest the semiquantitative scoring system is valid for assessing perimeniscal synovitis. The relationship between meniscal pathology and adjacent synovitis requires further study.

Aged↗
PubMed2006

Preliminary evidence for a structural benefit of the new bisphosphonate zoledronic acid in early rheumatoid arthritis.

OBJECTIVE: Bisphosphonates inhibit osteoclast activity, which is central to the development of bone damage in rheumatoid arthritis (RA). The aim of this study was to assess whether treatment with zoledronic acid, compared with placebo, could achieve a > or = 50% reduction in the development of new erosions on magnetic resonance imaging (MRI) in patients with early RA. METHODS: In this proof-of-concept study, 39 patients with early RA and clinical synovitis of the hand/wrist were randomized to receive infusions with either zoledronic acid (5 mg) or placebo, administered at baseline and week 13. Patients in both groups received methotrexate (MTX) at a dosage of 7.5-20 mg/week. MRI and plain radiography were performed at baseline and week 26. RESULTS: At week 26, the mean +/- SD change in MRI hand and wrist erosions was 61% lower in the zoledronic acid group compared with the placebo group (0.9 +/- 1.63 versus 2.3 +/- 3.09; P = 0.176). The mean +/- SD increase in the number of hand and wrist bones with erosions was 0.3 +/- 0.75 for zoledronic acid compared with 1.4 +/- 1.77 for placebo (P = 0.029). The proportion of patients in whom new MRI-visualized bone edema developed was smaller in the zoledronic acid group compared with the placebo group (33% versus 58%; P = 0.121). The zoledronic acid group had a mean change in the number of radiographic erosions of 0.1 compared with 0.5 for the placebo group (P = 0.677). The safety profile of zoledronic acid was similar to that of placebo. CONCLUSION: The results of this study suggest a structural benefit associated with zoledronic acid therapy in patients with RA, as demonstrated by consistent results in structural end points in favor of zoledronic acid plus MTX compared with MTX alone.

Adult↗
PubMed2006

Imaging outcomes and their role in determining outcomes in osteoarthritis and rheumatoid arthritis.

PURPOSE OF REVIEW: This review describes the advances in knowledge of outcomes that have occurred recently as a result of imaging research in both osteoarthritis and rheumatoid arthritis. RECENT FINDINGS: Recent imaging advances in osteoarthritis have offered insights into fundamental questions including the cause of pain and reasons for disease progression. Although ongoing disease modification clinical drug trials in osteoarthritis mostly use standardized plain radiographs to monitor structural changes in the joint, magnetic resonance imaging is rapidly evolving as a method of monitoring joint structure and with time may become the preferred method of monitoring this feature in osteoarthritis clinical trials. The past decade has seen major advances in the treatment of rheumatoid arthritis in which imaging determines whether individual agents or therapeutic regimens are structure modifying. Although conventional radiography remains the gold standard for assessing structural progression in rheumatoid arthritis, growing work on the performance metrics of magnetic resonance imaging has resulted in its increasing use in trials. Ultrasonography shows preliminary promise as a useful outcome measure. SUMMARY: Recent advances in imaging are improving our understanding of the etiopathogenesis and treatment of persons with osteoarthritis and rheumatoid arthritis. Complex challenges face us over the coming years as clinicians and researchers grapple with the use of these new techniques, the insights they may provide, and their clinical application.

Arthritis, Rheumatoid↗
PubMed2005

Effect of risedronate on joint structure and symptoms of knee osteoarthritis: results of the BRISK randomized, controlled trial [ISRCTN01928173].

To determine the efficacy and safety of risedronate in patients with knee osteoarthritis (OA), the British study of risedronate in structure and symptoms of knee OA (BRISK), a 1-year prospective, double-blind, placebo-controlled study, enrolled patients (40-80 years of age) with mild to moderate OA of the medial compartment of the knee. The primary aims were to detect differences in symptoms and function. Patients were randomized to once-daily risedronate (5 mg or 15 mg) or placebo. Radiographs were taken at baseline and 1 year for assessment of joint-space width using a standardized radiographic method with fluoroscopic positioning of the joint. Pain, function, and stiffness were assessed using the Western Ontario and McMaster Universities (WOMAC) OA index. The patient global assessment and use of walking aids were measured and bone and cartilage markers were assessed. The intention-to-treat population consisted of 284 patients. Those receiving risedronate at 15 mg showed improvement of the WOMAC index, particularly of physical function, significant improvement of the patient global assessment (P < 0.001), and decreased use of walking aids relative to patients receiving the placebo (P = 0.009). A trend towards attenuation of joint-space narrowing was observed in the group receiving 15 mg risedronate. Eight percent (n = 7) of patients receiving placebo and 4% (n = 4) of patients receiving 5 mg risedronate exhibited detectable progression of disease (joint-space width >or= 25% or >or= 0.75 mm) versus 1% (n = 1) of patients receiving 15 mg risedronate (P = 0.067). Risedronate (15 mg) significantly reduced markers of cartilage degradation and bone resorption. Both doses of risedronate were well tolerated. In this study, clear trends towards improvement were observed in both joint structure and symptoms in patients with primary knee OA treated with risedronate.

Adult↗
PubMed2005

Very early treatment with infliximab in addition to methotrexate in early, poor-prognosis rheumatoid arthritis reduces magnetic resonance imaging evidence of synovitis and damage, with sustained benefit after infliximab withdrawal: results from a twelve-month randomized, double-blind, placebo-controlled trial.

OBJECTIVE: Anti-tumor necrosis factor alpha agents are among the most effective therapies for rheumatoid arthritis (RA). However, their optimal use is yet to be determined. This 12-month double-blind study attempted remission induction using standard therapy with or without infliximab in patients with early, poor-prognosis RA. The primary end point was synovitis (measured by magnetic resonance imaging [MRI]). Clinical observations continued to 24 months. METHODS: All patients had fewer than 12 months of symptoms. Assessments included full metrologic evaluation, laboratory tests, radiographs, functional evaluation using the Health Assessment Questionnaire (HAQ), and quality of life measurement using the RA Quality of Life (RAQoL) questionnaire. MRI was performed at 0, 4, 14, and 54 weeks; MR images were scored blindly. Patients received methotrexate (MTX) and were randomized to receive either infliximab or placebo for 12 months. RESULTS: Twenty patients were recruited (mean age 52 years, mean symptom duration 6 months, mean C-reactive protein level 42 mg/liter, and 65% rheumatoid factor positive). At 1 year, all MRI scores were significantly better, with no new erosions in the infliximab plus MTX group; a greater percentage of infliximab plus MTX-treated patients fulfilled the American College of Rheumatology (ACR) 50% and 70% improvement criteria (78% versus 40% in the placebo plus MTX group and 67% versus 30%, respectively) and had a greater functional benefit (P < 0.05 for all comparisons). Importantly, at 1 year after stopping induction therapy, response was sustained in 70% of the patients in the infliximab plus MTX group, with a median Disease Activity Score in 28 joints (DAS28) of 2.05 (remission range). At 2 years, there were no significant between-group differences in the DAS28, ACR response, or radiographic scores, but differences in the HAQ and RAQoL scores were maintained (P < 0.05). CONCLUSION: Remission induction with infliximab plus MTX provided a significant reduction in MRI evidence of synovitis and erosions at 1 year. At 2 years, functional and quality of life benefits were sustained, despite withdrawal of infliximab therapy. These data may have significant implications for the optimal use of expensive biologic therapies.

Antibodies, Monoclonal↗
PubMed2005

MRI and musculoskeletal ultrasonography as diagnostic tools in early arthritis.

Rheumatoid arthritis (RA) is a chronic and progressive inflammatory disorder primarily affecting the synovium and is characterized by destruction of bone and cartilage. Early diagnosis and treatment of RA can improve disease outcomes substantially. Magnetic resonance imaging and musculoskeletal ultrasonography may facilitate early diagnosis and aid the targeting of intensive therapy. Magnetic resonance imaging and musculoskeletal ultrasonography also are able to monitor temporal changes in disease activity (ie, synovitis) and damage (ie, erosions). These imaging modalities are likely to be increasingly used in the management of early rheumatoid arthritis to ensure the best patient outcomes, although more work is required to determine their optimal roles.

Arthritis↗
PubMed2005

The evidence for magnetic resonance imaging as an outcome measure in proof-of-concept rheumatoid arthritis studies.

Magnetic resonance imaging (MRI) has now been used extensively in cross-sectional and observational studies as well as in controlled clinical trials to assess disease activity and joint damage in rheumatoid arthritis (RA). MRI measurements or scores for erosions, bone edema, and synovitis have been developed and validated by several groups. The OMERACT criteria require that outcome measures demonstrate adequate validity, discriminative power, and feasibility if they are to be useful in clinical trials. Specific performance targets for these criteria depend on the scientific, regulatory, logistical, and financial context of the study in question. We review the extent to which MRI assessments of joint erosion, bone edema, and synovitis fulfil these criteria, particularly as they relate to proof-of-concept RA clinical trials.

Arthritis, Rheumatoid↗
PubMed2005

Musculoskeletal ultrasound including definitions for ultrasonographic pathology.

Ultrasound (US) has great potential as an outcome in rheumatoid arthritis trials for detecting bone erosions, synovitis, tendon disease, and enthesopathy. It has a number of distinct advantages over magnetic resonance imaging, including good patient tolerability and ability to scan multiple joints in a short period of time. However, there are scarce data regarding its validity, reproducibility, and responsiveness to change, making interpretation and comparison of studies difficult. In particular, there are limited data describing standardized scanning methodology and standardized definitions of US pathologies. This article presents the first report from the OMERACT ultrasound special interest group, which has compared US against the criteria of the OMERACT filter. Also proposed for the first time are consensus US definitions for common pathological lesions seen in patients with inflammatory arthritis.

Arthritis, Rheumatoid↗