Prospects for Therapies in Osteoarthritis

Osteoarthritis (OA) is a chronic, debilitating disease affecting millions of people worldwide. Management of OA involves pharmacological and non-pharmacological approaches. Conventional pharmacological treatments have limited efficacy and are associated with a number of side-effects, restricting the number of patients who can use them. New pharmacological therapies for managing OA are required and a number have been developed targeting different tissues in OA: bone and cartilage, synovium and nerves. However, there has been overall limited success. Disease-modifying osteoarthritis drugs (DMOADs) are a putative class of therapies aimed at improving OA structural pathologies and consequent symptoms. Recent DMOAD studies have demonstrated some promising therapies but also provided new considerations for future trials

The prevalence and impact of self-reported foot and ankle pain in the over 55 age group: A secondary data analysis from a large community sample

Background: While the prevalence and impact of musculoskeletal problems are high, most attention has been directed towards the back, knee and hip disorders. Foot pain is known to be common in older adults and accounts for a significant burden on health services. The aim of this study was to assess the impact of foot and ankle joint pain, considering age, presence of co-morbidities and other site joint pain, in a large community sample. Methods: In the North Yorkshire Health study, 16,222 people over 55 years participated in a detailed survey of the prevalence and impact of lower limb joint problems. Self-assessment of overall body pain and functional activities of daily living were assessed. Participants indicated the presence of joint pain, stiffness or swelling during the last 3 months which had lasted for more than 6 weeks on a manikin: data were captured on the foot and the ankle. Results: The prevalence of self-reported foot and ankle joint pain was substantial: 184.33 per 1000, second only to knee problems. While foot pain was common, it was mostly associated with joint pain at other sites; only 1 in 11 of those with foot and ankle pain reported it only in the foot. Logistic regression modeling revealed while established factors such as co-morbidities, knee and hip problems contributed to functional impairment, foot and ankle problems contributed to an additional increased risk of having difficulty standing and walking by two fold (OR = 2.314, 95%CI 2.061–2.598), going up and down stairs by 71% (OR = 1.711, 95%CI 1.478–1.980) and getting up from a seated position by 44% (OR = 1.438, 95%CI 1.197–1.729). Conclusion: These results suggest that not only are foot problems in the over 55 age group extremely prevalent, they have a considerable impact on functional abilities

The dynamics of response as measured by multiple composite outcome tools in the TIght COntrol of inflammation in early Psoriatic Arthritis (TICOPA) trial

Background: We aimed to evaluate the dynamics of treatment response with different composite measures in the TIght COntrol of inflammation in early Psoriatic Arthritis (TICOPA) trial. Methods: Participants with early disease-modifying antirheumatic drug-naïve psoriatic arthritis (PsA) were randomised 1:1 to either tight control (TC; 4 weekly review with therapy escalation if criteria not met) or standard care (SC; 12 weekly review). We calculated modified versions of the Psoriatic ArthritiS Disease Activity Score (PASDAS), Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) Composite scorE (GRACE) and Composite Psoriatic Disease Activity Index (CPDAI) at baseline and 12 weekly to 48 weeks by blinded assessor. For missing data, we used the last observation carried forward. Comparison between groups was made by analysis of covariance and comparison of area under the curve (AUC). Results: 206 people were randomised to TC (n=101) or SC (n=105). Significant differences between treatment groups were seen (p<0.0001 for all composite measures). AUC analysis demonstrated a significant difference between groups for the PASDAS but not GRACE and CPDAI. For participants with oligoarthritis, a significant difference between groups was seen for each measure, although the significance levels were greatly diminished (PASDAS, p=0.04; GRACE p=0.01; CPDAI p=0.04). For oligoarthritis using AUC analysis, none of the measures could distinguish between groups. Conclusions: Composite measures of disease activity were able to distinguish between TICOPA treatment arms, although differences were diminished for those with oligoarthritis. Further data are needed to inform the preferred composite measure for use as the primary outcome in PsA trials

A Home Exercise Programme Is No More Beneficial than Advice and Education for People with Neurogenic Claudication: Results from a Randomised Controlled Trial

Objective: To compare the effectiveness of a physiotherapy programme with a control treatment of advice and education in patients with neurogenic claudication symptoms. Design: Pragmatic randomised controlled clinical trial. Setting: Primary care-based musculoskeletal service. Patients: Adults aged 50 or over with neurogenic claudication symptoms causing limitation of walking. Interventions: Condition-specific home exercises combined with advice and education, or advice and education alone. Main outcome measures: The primary outcome was the difference in improvement of symptom severity scores on the Swiss Spinal Stenosis Scale at eight weeks. Secondary outcomes included measures of physical function, pain and general well-being at eight weeks and 12 months. Results: There was no significant difference between groups in the Swiss Spinal Stenosis symptom severity scale at eight weeks (t = 0.47, p = 0.643): mean change (SD) control group -0.18 (0.47), treatment group -0.10 (0.66), difference (95% CI) 0.08 (-0.19, 0.35); baseline-adjusted difference 0.06 (-0.19, 0.31)]. An unplanned subgroup analysis suggested that for patients with the top 25% of baseline symptom severity scores, the physiotherapy exercise programme resulted in an improvement in the primary outcome, and modest but consistently better secondary outcomes at both time-points compared to the control group. The effectiveness in different subgroups requires further direct evaluation. Conclusions: In the treatment of patients with neurogenic claudication symptoms, a physiotherapist-prescribed home exercise programme is no more effective than advice and education

The effect of targeted treatment on people with patellofemoral pain: A pragmatic, randomised controlled feasibility study

Background: Targeted treatment, matched according to specific clinical criteria e.g. hip muscle weakness, may result in better outcomes for people with patellofemoral pain (PFP). However, to ensure the success of future trials, a number of questions on the feasibility of a targeted treatment need clarification. The aim of the study was to explore the feasibility of matched treatment (MT) compared to usual care (UC) management for a subgroup of people with PFP determined to have hip weakness and to explore the mechanism of effect for hip strengthening. Methods: In a pragmatic, randomised controlled feasibility study, 24 participants with PFP (58% female; mean age 29 years) were randomly allocated to receive either MT aimed specifically at hip strengthening, or UC over an eight-week period. The primary outcomes were feasibility outcomes, which included rates of adherence, attrition, eligibility, missing data and treatment efficacy. Secondary outcomes focused on the mechanistic outcomes of the intervention, which included hip kinematics. Results: Conversion to consent (100%), missing data (0%), attrition rate (8%) and adherence to both treatment and appointments ( > 90%) were deemed successful endpoints. The analysis of treatment efficacy showed that the MT group reported a greater improvement for the Global Rating of Change Scale (62% vs. 9%) and the Anterior Knee Pain Scale (-5.23 vs. 1.18) but no between-group differences for either average or worst pain. Mechanistic outcomes showed a greatest reduction in peak hip internal rotation angle for the MT group (13.1% vs. -2.7%). Conclusion: This feasibility study indicates that a definitive randomised controlled trial investigating a targeted treatment approach is achievable. Findings suggest the mechanism of effect of hip strengthening may be to influence kinematic changes in hip function in the transverse plane

Understanding patterns of care for musculoskeletal patients using routinely collected National Health Service data from general practices in England

Musculoskeletal conditions are extremely common and represent a costly and growing problem in the United Kingdom. Understanding patterns of care and how they vary between individual patients and patient groups is necessary for effective and efficient disease management. In this article, we present a novel approach to understanding patterns of care for musculoskeletal patients in which trajectories are constructed from clinical and administrative data that are routinely collected by clinicians and healthcare professionals. Our approach is applied to routinely collected National Health Service data for musculoskeletal patients who were registered to a set of general practices in England and highlights both known and previously unreported variations in the prescribing of opioid analgesics by gender and presence of pre-existing depression. We conclude that the application of our approach to routinely collected National Health Service data can extend the dimensions over which patterns of care can be understood for musculoskeletal patients and for patients with other long-term conditions

The dynamics of response as measured by multiple composite outcome tools in the TIght COntrol of inflammation in early Psoriatic Arthritis (TICOPA) trial

Background: We aimed to evaluate the dynamics of treatment response with different composite measures in the TIght COntrol of inflammation in early Psoriatic Arthritis (TICOPA) trial. Methods: Participants with early disease-modifying antirheumatic drug-naïve psoriatic arthritis (PsA) were randomised 1:1 to either tight control (TC; 4 weekly review with therapy escalation if criteria not met) or standard care (SC; 12 weekly review). We calculated modified versions of the Psoriatic ArthritiS Disease Activity Score (PASDAS), Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) Composite scorE (GRACE) and Composite Psoriatic Disease Activity Index (CPDAI) at baseline and 12 weekly to 48 weeks by blinded assessor. For missing data, we used the last observation carried forward. Comparison between groups was made by analysis of covariance and comparison of area under the curve (AUC). Results: 206 people were randomised to TC (n=101) or SC (n=105). Significant differences between treatment groups were seen (p<0.0001 for all composite measures). AUC analysis demonstrated a significant difference between groups for the PASDAS but not GRACE and CPDAI. For participants with oligoarthritis, a significant difference between groups was seen for each measure, although the significance levels were greatly diminished (PASDAS, p=0.04; GRACE p=0.01; CPDAI p=0.04). For oligoarthritis using AUC analysis, none of the measures could distinguish between groups. Conclusions: Composite measures of disease activity were able to distinguish between TICOPA treatment arms, although differences were diminished for those with oligoarthritis. Further data are needed to inform the preferred composite measure for use as the primary outcome in PsA trials

Obesity and rates of clinical remission and low MRI inflammation in rheumatoid arthritis

Objectives: Obesity has been proposed as a risk factor for refractory rheumatoid arthritis (RA). We evaluated the impact of obesity on achieving clinical and imaging definitions of low disease activity. Methods: This study evaluated 470 patients with RA from GO-BEFORE and GO-FORWARD randomised clinical trials. Included patients had blinded clinical disease activity measures and MRI at baseline, 24 and 52 weeks. Synovitis, osteitis and total inflammation scores were determined using the RA MRI scoring system. Multivariable logistic regression analyses compared odds of achieving Disease Activity Score using 28 joints and C-reactive protein (DAS28-CRP) remission, low component measures, or low MRI inflammation measures at 24 weeks in patients with obesity versus no obesity. Results: At 24 weeks, patients with obesity were significantly less likely to achieve DAS28(CRP) remission (OR 0.47; 95% CI 0.24 to 0.92, p=0.03). In contrast, patients with obesity had similar odds of achieving low synovitis (OR 0.94; 95% CI 0.51 to 1.72, p=0.84) and inflammation scores (OR 1.16; 95% CI 0.61 to 2.22, p=0.64) and greater odds of achieving low osteitis scores (OR 2.06; 95% CI 1.10 to 3.84, p=0.02) versus normal weight patients. Conclusions: Patients with RA and obesity have lower rates of DAS28 remission but similar rates of low MRI activity compared with patients without obesity, suggesting that obesity and its associated comorbidities can bias clinical disease activity measures. Trial registration number: NCT00361335 and NCT00264550; Post-results

Marked and Rapid Change of Bone Shape In Acutely Acl Injured Knees – An Exploratory Analysis Of The Kanon Trial

Background To investigate changes in knee 3D bone shape over the first 5 years after acute anterior cruciate ligament (ACL) injury in participants of the randomized controlled KANON-trial. Methods Serial MR images over 5 years from 121 young (32 women, mean age 26.1 years) adults with an acute ACL tear in a previously un-injured knee were analyzed using statistical shape models for bone. A matched reference cohort of 176 individuals was selected from the Osteoarthritis Initiative (OAI). Primary endpoint was change in bone area of the medial femoral condyle; exploratory analyses compared results by treatment and examined other knee regions. Comparisons were made using repeated measures mixed model ANOVA with adjustment for age, sex and BMI. Results Mean medial femur bone area increased 3.2% (78.0 [95% CI 70.2 to 86.4] mm2) over 5 years after ACL injury and most prominently in knees treated with ACL reconstruction. A higher rate of increase occurred over the first two years compared to the latter three-years (66.2 [59.3 to 73.2] vs. 17.6 [12.2 to 23.0] mm2) and was 6.7 times faster than in the reference cohort. The pattern and location of shape change in the extrapolated KANON data was very similar to that observed in another knee-osteoarthritis cohort. Conclusion 3D shape modelling after acute ACL injury revealed rapid bone shape changes, already evident at 3 months. The bone-change pattern after ACL injury demonstrated flattening and bone growth on the outer margins of the condyles similar to that reported in established knee osteoarthritis