23 research outputs found
Effect of a treatment strategy utilising golimumab, methotrexate and corticosteroids versus methotrexate and corticosteroids in early, untreated psoriatic arthritis (GOLMePsA): a single-centre, double-blind, parallel-group, randomised controlled trial
No full textBackground: The optimal treatment strategy in early psoriatic arthritis remains unknown. We aimed to assess whether the combination of methotrexate and golimumab plus corticosteroids is superior to methotrexate plus corticosteroids in reducing disease activity in early, untreated psoriatic arthritis.
Methods: We did a double-blind, randomised, placebo-controlled, parallel-group, single-centre study in adults with treatment-naïve active psoriatic arthritis. Participants were required to have been diagnosed up to 24 months before enrolment and had to be naïve to conventional synthetic, biologic, or targeted synthetic disease-modifying antirheumatic drugs or systemic treatments before enrolment. Participants were randomly assigned (1:1) to receive either combination therapy of golimumab and methotrexate or placebo and methotrexate, stratified by the number of involved peripheral joints at baseline. Investigators and participants were masked to treatment allocation. At baseline, all participants received methylprednisolone (120 mg intramuscular administration, single dose) and commenced weekly methotrexate (increased to 25 mg within 28 days). Golimumab or placebo were administered by subcutaneous injections every 4 weeks. By week 24, additional methylprednisolone was permitted once (totalling up to 240 mg exposure). The primary endpoint was the difference in mean Psoriatic Arthritis Disease Activity Score (PASDAS) at week 24 in the intention-to-treat population, compared using analysis of covariance via multiple linear regression. People with lived experience of psoriatic arthritis were involved in the design and conduct the study. The study was registered with EudraCT, 2013-004122-28, and is complete.
Findings: Between Nov 3, 2015 and Jan 26, 2022, 106 people were assessed for eligibility, 22 were excluded, and 84 were randomly assigned (43 to the golimumab and methotrexate group and 41 to the placebo and methotrexate group). 46 (55%) participants were male and 38 (45%) were female. The mean age was 42·5 years (SD 12·4) and 61 (73%) participants were White and seven (8%) were from any Asian, Black, or other ethnic background. PASDAS did not differ between treatment groups at week 24 (unadjusted mean 3·09 [SD 1·32] in the placebo and methotrexate group and 2·70 [1·38] in the golimumab and methotrexate group; adjusted difference –0·55 [95% CI –1·12 to 0·03]; p=0·064). More participants in the placebo and methotrexate group received additional corticosteroids before week 24 (20 [49%] of 41 vs nine [21%] of 43; odds ratio 0·28 [95% CI 0·11 to 0·72]; p=0·009). Similar numbers of participants had adverse events (38 [93%] of 41 in the placebo and methotrexate group vs 41 [95%] of 43 in the golimumab and methotrexate group; risk difference 0·03 [95% CI –0·09 to 0·15]), although altered laboratory investigations and infections occurred more frequently in the golimumab and methotrexate group. No deaths, serious, or unexpected adverse events occurred.
Interpretation: Both interventions led to improved disease activity in patients with early, untreated psoriatic arthritis, without a clinically or statistically significant difference in PASDAS between treatment groups at week 24. Participants in the placebo and methotrexate group required more rescue corticosteroids. Sustained results were observed at week 52 in both groups, without serious or unexpected adverse events
RIPOSTE: A framework for improving the design and analysis of laboratory-based research
No full textLack of reproducibility is an ongoing problem in some areas of the biomedical sciences. Poor experimental design and a failure to engage with experienced statisticians at key stages in the design and analysis of experiments are two factors that contribute to this problem. The RIPOSTE (Reducing IrreProducibility in labOratory STudiEs) framework has been developed to support early and regular discussions between scientists and statisticians in order to improve the design, conduct and analysis of laboratory studies and, therefore, reduce irreproducibility. This framework is intended for use during the early stages of a research project, when specific questions or hypotheses are proposed. The essential points within the framework are explained and illustrated using three examples (a medical equipment test, a macrophage study and a gene expression study). Sound study design minimises the possibility of bias being introduced into experiments and leads to higher quality research with more reproducible results
How do people with knee osteoarthritis use osteoarthritis pain medications and does this change over time? Data from the Osteoarthritis Initiative.
No full textIntroduction: The aim of this analysis was to describe comprehensively the cross-sectional and longitudinal patterns of analgesic and nutraceutical medication use for knee osteoarthritis (OA) in a contemporary US cohort and to investigate associated demographic and clinical factors. Methods: Baseline, 12, 24 and 36 month data were obtained retrospectively from the National Institutes of Health Osteoarthritis Initiative. Participants had symptomatic radiographic knee OA. Multiple binary logistic regression models identified characteristics independently associated with the use of analgesics or nutraceuticals. Results: We included 987 subjects (55.9% female, mean age 61.5 years, 71.0% white). At baseline, 68.2% reported frequent use of a conventional analgesic or nutraceutical for joint pain (for more than half of the previous month). Non-prescription non-steroidal anti-inflammatory drugs (NSAIDs) were the most frequently reported medications (26.8%), even in those more than 75-years old. Multiple conventional analgesics were used by 11.9%. Frequent analgesic use was more likely in women (odds ratio (OR) 1.8 (95% confidence interval (CI) 1.3 to 2.3)) and people with more pain (moderate 1.7 (1.2 to 2.4); severe 3.1 (2.1 to 4.7)); nutraceutical use was less likely in non-whites (0.4 (0.3 to 0.6)), those more than 74-years old (0.6 (0.3 to 0.9)) and those with comorbidities (0.6 (0.5 to 0.9)) and more likely in people with Kellgren-Lawrence (KL) grade 4 (2.2 (1.5 to 3.3)). Overall there was no change in the proportion of participants frequently using prescription or over the counter (OTC) analgesics at 36 months, although most people had changed medication type; of those using a traditional analgesic at baseline approximately one third were still using the same type at 36 months (ranging from 26.2% of baseline prescription NSAID users to 40.6% of baseline acetaminophen users). All participants reporting baseline analgesic use also reported 36 month analgesic use. Female participants (OR 95% CI 1.2 to 3.2, P = 0.009), those with high body mass index (1.2 to 4.8, P = 0.010) and those with moderate (1.6 to 2.6, P = 0.090) or severe (1.8 to 12.0, P = 0.002) baseline pain were more likely to use pain medication during the 36 month follow-up period; participants more than 75-years old were less likely (0.2 to 1.0, P = 0.053). CONCLUSIONS: Most people with knee OA used pharmacological therapies frequently, and use appeared to be according to American College of Rheumatology recommendations. Change in medication type used was common. Persistent non-prescription NSAID use in older people is an area of concern
MRI Inflammation of the Hand Interosseous Tendons occurs in anti-CCP positive at-risk individuals and may precede the development of clinical synovitis
No full textObjectives
To investigate, by MRI, ITI in anti-cyclic citrullinated peptide (CCP)-positive at-risk individuals (CCP +at risk) and to describe the anatomy, prevalence and clinical associations across the RA continuum.
Methods
Hand MRI was performed in 93 CCP + at risk, 47 early RA (ERA), 28 established ‘late’ RA (LRA) and 20 healthy controls (HC) and scored for ITI, flexor tenosynovitis (TSV) and RA MRI scoring at the metacarpophalangeal joints (MCPJs). Cadaveric and histological studies were performed to explore the anatomical basis for MRI ITI.
Results
The proportion of subjects with ITI and the number of inflamed interosseous tendons (ITs) increased along the disease continuum (p<0.001): 19% of CCP +at risk, 49% of ERA and 57% of LRA had ≥1 IT inflamed . ITI was not found in any HC. ITI was more frequently identified in tender MCPJs compared with nontender MCPJs (28% vs 12%, respectively). No IT tenosynovial sheath was identified in cadavers on dissection or histological studies suggesting MRI findings represent peritendonitis. Dye studies indicated no communication between the IT and the joint.
Conclusions
ITI occurs in CCP + at-risk individuals and can precede the onset of clinical synovitis. The ITs may be important nonsynovial extracapsular targets in the development and progression of RA
Toward the development of data-driven diagnostic subgroups for people with patellofemoral pain using modifiable clinical, biomechanical and imaging features
No full textBackground. Unfavourable treatment outcomes for people with patellofemoral pain (PFP) have been attributed to the potential existence of subgroups that respond differently to treatment.
Objectives: This study aimed to identify subgroups within PFP by combining modifiable clinical, biomechanical and imaging features and exploring the prognosis of these subgroups.
Methods. Longitudinal cohort with baseline cluster analyses. Baseline data were analysed using a two-stage cluster analysis; 10 features were analysed within health domains before being combined at the second stage. Prognosis of the subgroups was assessed at 12-months with subgroup differences in the Global Rating of Change Scale analysed using an exploratory logistic regression adjusted for known confounders.
Results. 70 participants were included (mean age 31 years; 43 (61%) female). Cluster analysis revealed 4 subgroups: ‘Strong’, ‘Pronation & Malalignment’, ‘Weak’ and ‘Active & Flexible’. Descriptively, compared to the Strong subgroup (55% favourable), the odds of a favourable outcome were lower in the Weak subgroup (31% favourable; adjusted odds ratio [OR] 0.30; 95% confidence intervals [CI] 0.07, 1.36) and Pronation & Malalignment subgroup (50%; OR 0.64; 95% CI 0.11, 3.66),
and higher in the Active & Flexible subgroup (63%; OR 1.24 (95% CI 0.20, 7.51). Page 5 of 61 JOSPT, 1033 N. Fairfax St., Suite 304, Alexandria, VA 22314, ph. 877-766-3450 Journal of Orthopaedic & Sports Physical Therapy Review Copy Data-driven diagnostic subgroups in patellofemoral pain After adjustment, compared to the Strong subgroup, differences between some subgroups remained substantive but none were statistically significant
Conclusion. In this relatively small cohort, 4 PFP subgroups were identified which show potentially different outcomes at 12 months. Further research is required to determine whether a stratified treatment approach using these subgroups would improve outcomes for people with PF
PROspectiVe imaging research DEsign and coNducT (PROVIDENT): considerations for clinical trials and studies using imaging (Part II)
No full textObjectivesImaging is used in a wide range of contexts in clinical research projects, but adds complexity to the design, conduct and analysis. This paper is the second of two in which we use a consensus approach to combine multidisciplinary perspectives on the challenges in conducting prospective clinical trials and other research studies involving imaging. Here we consider challenges in image interpretation and quantification, quality assurance and quality control (QA/QC); scanner imaging acquisition, data flow and storage, health economics (HE) decision modelling, costings for running a trial; and commercialisation.Key findingsAvailability of scanners and staff can impact deliverability. Pre-specification of key procedures, roles and responsibilities via appropriate documentation is important; ensuring compatibility across different sites and machines is challenging and requires advance input from multiple stakeholders. Testing critical procedures, including the flow of images and derived data between participating sites and/or external legal entities, can avoid delays. Effective QA/QC is conducted at regular intervals; relevant staff should be involved at the planning stage. Identifying appropriately qualified readers and arranging for image hosting takes time; this should be done prior to image acquisition. Testing image interpretation burden informs feasibility and costings. Cost estimates for research involving imaging and HE modelling of imaging interventions can be complex due to the interplay between local and national policies, and the extent to which the research imaging is integrated with standard care.ConclusionThese considerations derived from a multidisciplinary team will be useful for funding applications, protocol design, trial implementation, conduct and commercialisation and uptake of new imaging techniques.Implications for practiceMany prospective imaging studies could be improved by the upfront awareness of potential challenges and understanding of real-world examples these considerations provide
PASDAS test-retest reliability in early, untreated PsA: data from the GOLMePsA clinical trial
No full textPASDAS has excellent test-retest reliability in early, untreated psoriatic arthritis
Muscle deterioration due to rheumatoid arthritis: Assessment by quantitative MRI and strength testing
No full textObjectives
RA patients often present with low muscle mass and decreased strength. Quantitative MRI offers a non-invasive measurement of muscle status. This study assessed whether MRI-based measurements of T2, fat fraction, diffusion tensor imaging and muscle volume can detect differences between the thigh muscles of RA patients and healthy controls, and assessed the muscle phenotype of different disease stages.
Methods
Thirty-nine RA patients (13 ‘new RA’—newly diagnosed, treatment naïve, 13 ‘active RA’—persistent DAS28 >3.2 for >1 year, 13 ‘remission RA’—persistent DAS28 1 year) and 13 age and gender directly matched healthy controls had an MRI scan of their dominant thigh. All participants had knee extension and flexion torque and grip strength measured.
Results
MRI T2 and fat fraction were higher in the three groups of RA patients compared with healthy controls in the thigh muscles. There were no clinically meaningful differences in the mean diffusivity. The muscle volume, handgrip strength, knee extension and flexion were lower in all three groups of RA patients compared with healthy controls.
Conclusion
Quantitative MRI and muscle strength measurements can potentially detect differences within the muscles between RA patients and healthy controls. These differences may be seen in RA patients who are yet to start treatment, those with persistent active disease, and those who were in clinical remission. This suggests that the muscles in RA patients are affected in the early stages of the disease and that signs of muscle pathology and muscle weakness are still observed in clinical remission
Improving the arthritis component of the SLEDAI-2K
No full textObjective
To propose a new definition for SLEDAI arthritis informed by imaging.
Methods
We performed a planned secondary analysis of observational data from a multicentre study evaluating SLE patients with inflammatory joint pain (swelling not required) using various clinical instruments, laboratory tests and ultrasound. For SLEDAI arthritis, assessors (blinded to ultrasound) were asked which of the glossary terms for arthritis in any version of the SLEDAI drove their decision to score for arthritis. These definitions were tested against ultrasound and other clinical variables. ROC analysis was used to test optimal joint count thresholds.
Results
A total of 78/133 patients had arthritis on SLEDAI-2K. In 21/78, clinician-observed swelling was not a reason for scoring (tenderness: 16/21; reported swelling between visits: 4/21; both of these: 1/21). No patient was scored for warmth or erythema alone. In total, 57 (73.1%) patients were scored for SLEDAI arthritis due to observed swelling, 90% had abnormal ultrasound (PPV = 90%, 95%CI: 79, 94). Of 21 patients with SLEDAI arthritis without observed swelling, 48% had abnormal ultrasound (PPV: 48%, 95%CI: 31, 67). Patients with SLEDAI arthritis with swelling had higher ESR, physician MSK-VAS, patient early morning stiffness (EMS)-VAS and IgG compared with other patients. Optimal sensitivity and specificity for ultrasound synovitis was 1 swollen joint using Youden’s criteria.
Conclusions
Our data suggest that the definition of arthritis in SLEDAI be modified to: ‘Inflammatory musculoskeletal pain (symmetrical small joint distribution), with one or more clinically swollen joints witnessed on examination, that is not explained by another arthropathy’
