Enthesitis in patients with psoriatic arthritis treated with secukinumab or adalimumab: a post hoc analysis of the EXCEED study.

OBJECTIVES: To evaluate enthesitis treatment response, including time to resolution and data from multiple enthesitis instruments, in patients with PsA treated with secukinumab or adalimumab for 52 weeks. METHODS: In this post hoc analysis of the EXCEED study, patients receiving secukinumab 300 mg or adalimumab 40 mg per the label were grouped by presence or absence of baseline enthesitis based on the Leeds Enthesitis Index (LEI) and the Spondyloarthritis Research Consortium of Canada Enthesitis Index (SPARCC). Efficacy was assessed according to several enthesitis-related instruments using non-responder imputation for the achievement of enthesitis resolution (LEI/SPARCC = 0), Kaplan-Meier analysis for time to resolution, and as-observed data for other outcomes. RESULTS: Enthesitis was present at baseline in 498 of 851 patients (58.5%) as assessed by LEI and in 632 of 853 patients (74.1%) as assessed by SPARCC. Patients with baseline enthesitis generally presented with greater disease activity. Similar proportions of patients receiving secukinumab or adalimumab achieved resolution of LEI and SPARCC at weeks 24 (secukinumab: LEI/SPARCC, 49.6%/45.8%; adalimumab: LEI/SPARCC, 43.6%/43.5%) and 52 (secukinumab: LEI/SPARCC, 60.7%/53.2%; adalimumab: LEI/SPARCC, 55.3%/51.4%), with comparable mean time to enthesitis resolution. Improvements were similar for both drugs at individual enthesitis sites. Resolution of enthesitis with secukinumab or adalimumab was associated with improvements in quality of life at week 52. CONCLUSION: Secukinumab and adalimumab showed similar efficacy, including time to resolution, with respect to resolution of enthesitis. Inhibition of IL-17 with secukinumab reduced clinical enthesitis similarly to TNF-α inhibition. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02745080.

Enhancing current guidance for psoriatic arthritis and its comorbidities: recommendations from an expert consensus panel.

OBJECTIVES: Existing guidelines for psoriatic arthritis (PsA) cover many aspects of management. Some gaps remain relating to routine practice application. An expert group aimed to enhance current guidance and develop recommendations for clinical practice that are complementary to existing guidelines. METHODS: A steering committee comprising experienced, research-active clinicians in rheumatology, dermatology and primary care agreed on themes and relevant questions. A targeted literature review of PubMed and Embase following a PICO framework was conducted. At a second meeting, recommendations were drafted and subsequently an extended faculty comprising rheumatologists, dermatologists, primary care clinicians, specialist nurses, allied health professionals, non-clinical academic participants and members of the Brit-PACT patient group, was recruited. Consensus was achieved via an online voting platform when 75% of respondents agreed in the range of 7-9 on a 9-point scale. RESULTS: The guidance comprised 34 statements covering four PsA themes. Diagnosis focused on strategies to identify PsA early and refer appropriately, assessment of diagnostic indicators, use of screening tools and use of imaging. Disease assessment centred on holistic consideration of disease activity, physical functioning and impact from a patient perspective, and on how to implement shared decision-making. For comorbidities, recommendations included specific guidance for high-impact conditions such as depression and obesity. Management statements (which excluded extant guidance on pharmacological therapies) covered multidisciplinary team working, implementation of lifestyle modifications and treat-to-target strategies. Minimising corticosteroid use was recommended where feasible. CONCLUSION: The consensus group have made evidence-based best practice recommendations for the management of PsA to enhance the existing guidelines.

EULAR recommendations for the use of imaging in the clinical management of peripheral joint osteoarthritis.

The increased information provided by modern imaging has led to its more extensive use. Our aim was to develop evidence-based recommendations for the use of imaging in the clinical management of the most common arthropathy, osteoarthritis (OA). A task force (including rheumatologists, radiologists, methodologists, primary care doctors and patients) from nine countries defined 10 questions on the role of imaging in OA to support a systematic literature review (SLR). Joints of interest were the knee, hip, hand and foot; imaging modalities included conventional radiography (CR), MRI, ultrasonography, CT and nuclear medicine. PubMed and EMBASE were searched. The evidence was presented to the task force who subsequently developed the recommendations. The strength of agreement for each recommendation was assessed. 17 011 references were identified from which 390 studies were included in the SLR. Seven recommendations were produced, covering the lack of need for diagnostic imaging in patients with typical symptoms; the role of imaging in differential diagnosis; the lack of benefit in monitoring when no therapeutic modification is related, though consideration is required when unexpected clinical deterioration occurs; CR as the first-choice imaging modality; consideration of how to correctly acquire images and the role of imaging in guiding local injections. Recommendations for future research were also developed based on gaps in evidence, such as the use of imaging in identifying therapeutic targets, and demonstrating the added value of imaging. These evidence-based recommendations and related research agenda provide the basis for sensible use of imaging in routine clinical assessment of people with OA.

EULAR recommendations for the non-pharmacological core management of hip and knee osteoarthritis.

The objective was to develop evidence -based recommendations and a research and educational agenda for the non-pharmacological management of hip and knee osteoarthritis (OA). The multidisciplinary task force comprised 21 experts: nurses, occupational therapists, physiotherapists, rheumatologists, orthopaedic surgeons, general practitioner, psychologist, dietician, clinical epidemiologist and patient representatives. After a preliminary literature review, a first task force meeting and five Delphi rounds, provisional recommendations were formulated in order to perform a systematic review. A literature search of Medline and eight other databases was performed up to February 2012. Evidence was graded in categories I-IV and agreement with the recommendations was determined through scores from 0 (total disagreement) to 10 (total agreement). Eleven evidence-based recommendations for the non-pharmacological core management of hip and knee OA were developed, concerning the following nine topics: assessment, general approach, patient information and education, lifestyle changes, exercise, weight loss, assistive technology and adaptations, footwear and work. The average level of agreement ranged between 8.0 and 9.1. The proposed research agenda included an overall need for more research into non-pharmacological interventions for hip OA, moderators to optimise individualised treatment, healthy lifestyle with economic evaluation and long-term follow-up, and the prevention and reduction of work disability. Proposed educational activities included the required skills to teach, initiate and establish lifestyle changes. The 11 recommendations provide guidance on the delivery of non-pharmacological interventions to people with hip or knee OA. More research and educational activities are needed, particularly in the area of lifestyle changes.

Significant improvement in synovitis, osteitis, and bone erosion following golimumab and methotrexate combination therapy as compared with methotrexate alone: a magnetic resonance imaging study of 318 methotrexate-naive rheumatoid arthritis patients.

OBJECTIVE: To evaluate the effects of golimumab on inflammation/structural damage detected by magnetic resonance imaging (MRI) in patients with rheumatoid arthritis (RA). METHODS: Methotrexate (MTX)-naive RA patients (n = 637) were randomized to placebo plus MTX, golimumab 100 mg plus placebo, golimumab 50 mg plus MTX, or golimumab 100 mg plus MTX (subcutaneous golimumab every 4 weeks). Of these, 318 patients participated in an MRI substudy. MRIs (contrast-enhanced; 1.5T) of the wrist and second through fifth metacarpophalangeal joints of the dominant hand were obtained at baseline and weeks 12 and 24. MRIs were scored by 2 independent readers (blinded to image sequence/chronology, patient identity, and treatment group) for synovitis, bone edema/osteitis, and bone erosions using the Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS) system. Radiographs (hands, wrists, forefeet at baseline and week 28) were scored by 2 other readers (blinded as above) using the modified Sharp/van der Heijde (SvdH) scoring system. Changes from baseline were compared between treatment groups (two-sided analysis of variance on van der Waerden normal scores). RESULTS: At weeks 12 and 24, combined therapy with golimumab plus MTX versus placebo plus MTX significantly improved RAMRIS scores for synovitis (mean -1.92 versus 0.14 [P < 0.001] at week 12; -2.45 versus -1.04 [P < 0.001] at week 24), osteitis (mean -1.82 versus 0.56 [P < 0.001] at week 12; -2.27 versus -0.32 [P < 0.001] at week 24), and bone erosion (mean -0.40 versus 0.24 [P = 0.016] at week 12; -0.40 versus -0.24 [P = 0.010] at week 24). Results of sensitivity analyses (no missing doses/data and using linear extrapolation) were generally consistent with results of the primary analyses. Changes in SvdH scores among the MRI substudy patients at week 28 showed no significant difference between golimumab plus MTX therapy and placebo plus MTX (mean 0.49 versus 0.92; P = 0.19). Radiographic SvdH scores demonstrated inhibition of structural damage progression by treatment with golimumab plus MTX as compared with placebo plus MTX in the overall study population but required double the number of patients (637 versus 318) and double the length of followup (28 versus 12 weeks) as needed for MRI to demonstrate this. CONCLUSION: Improvements in inflammation (synovitis and osteitis) and erosions with golimumab plus MTX therapy exceeded those with placebo plus MTX therapy from week 12 onward, confirming the overall clinical/radiologic findings. MRI was more sensitive than conventional radiography in detecting the progression of erosions.

Prediction of flare following remission and treatment withdrawal in early rheumatoid arthritis: post hoc analysis of a phase IIIb trial with abatacept.

BACKGROUND: Drug-free remission is a desirable goal in rheumatoid arthritis (RA) for both patients and clinicians. The aim of this post hoc analysis was to investigate whether clinical and magnetic resonance imaging (MRI) variables in patients with early RA who achieved remission with methotrexate and/or abatacept at 12 months could predict disease flare following treatment withdrawal. METHODS: In the AVERT study of abatacept in early RA, patients with low disease activity at month 12 entered a 12-month period with all treatment discontinued (withdrawal, WD). This post hoc analysis assessed predictors of disease flare at WD+6months (mo) and WD+12mo of patients with Disease Activity Score in 28 joints (DAS28)-defined remission (DAS28[C-reactive protein (CRP)] <2.6) at withdrawal using univariate and multivariable regression models. Predictors investigated included the Health Assessment Questionnaire-Disability Index (HAQ-DI), pain, Patient Global Assessment; MRI synovitis, erosion, bone edema, and combined (synovitis + bone edema) inflammation scores. RESULTS: Remission was achieved by 172 patients; 100 (58%) and 113 (66%) patients had experienced a flare at WD+6mo and WD+12mo, respectively. In univariate analyses, higher HAQ-DI and MRI synovitis, erosion, bone edema, and combined inflammation scores at WD were identified as potential predictors of flare (P ≤ 0.01). In multivariable analysis, high scores at WD for HAQ-DI and MRI erosion were confirmed as independent predictors of flare at WD+6mo and WD+12mo (P < 0.01). CONCLUSION: In patients with early RA achieving clinical remission, patient function (HAQ-DI), and MRI measures of bone damage (erosion) predicted disease flare 6 and 12 months after treatment withdrawal. These variables may help identify patients with early RA in clinical remission as candidates for successful treatment withdrawal. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01142726 (date of registration: June 11, 2010).

Assessment by MRI of inflammation and damage in rheumatoid arthritis patients with methotrexate inadequate response receiving golimumab: results of the GO-FORWARD trial.

OBJECTIVE: To evaluate golimumab's effect on MRI-detected inflammation and structural damage in patients with active rheumatoid arthritis (RA) despite methotrexate (MTX). METHODS: Patients (n=444) were randomly assigned to placebo plus MTX, golimumab 100 mg plus placebo, golimumab 50 mg plus MTX, or golimumab 100 mg plus MTX (subcutaneous injections every 4 weeks). A subset of 240 patients participated in an MRI substudy. MRIs (1.5T+contrast enhancement) of the dominant wrist and metacarpophalangeal (MCP) joints were obtained at baseline and weeks 12 and 24. Images were scored by two independent, blinded readers for synovitis (0-9 wrist only (n=240), 0-21 wrist+MCP (n=223)), bone oedema (osteitis) (0-69) and bone erosions (0-230) using the OMERACT Rheumatoid Arthritis MRI Scoring system. RESULTS: Significant improvements in synovitis and bone oedema (osteitis) were observed in the combined golimumab plus MTX groups versus placebo plus MTX at week 12 (-1.77 vs -0.15, p<0.001 wrist+MCP and -2.00 vs 0.19, p=0.003, respectively) and week 24 (-1.91 vs -0.38, p<0.001 wrist+MCP and -1.74 vs 0.71, p=0.004, respectively). Fewer than 10% of patients had a substantial degree of erosive progression (most showed no progression) across all treatment groups (including the control group), precluding adequate evaluation of golimumab's effect on bone erosions. CONCLUSION: Golimumab plus MTX significantly improved MRI-detected synovitis and osteitis (prognosticators of future structural damage) versus placebo plus MTX at weeks 12 and 24. The effect of golimumab on bone erosions could not be determined by semi-quantitative scoring in these RA patients with minimal progression of bone erosions.

Effects of walking with a shopping trolley on spinal posture and loading in subjects with neurogenic claudication.

OBJECTIVES: To explore possible mechanisms underpinning symptom relief and improved walking tolerance in patients with neurogenic claudication (NC) when pushing a shopping trolley by evaluating the effects of a shopping trolley on spinal posture and loading patterns. DESIGN: An exploratory study of kinematic and kinetic changes in walking with and without pushing a shopping trolley in persons with NC symptoms and a comparison with asymptomatic control subjects. SETTING: A primary care-based musculoskeletal service. PARTICIPANTS: Participants (n=8) with NC symptoms who have anecdotally reported symptomatic improvement when walking with a shopping trolley and a control group of asymptomatic persons (n=8). INTERVENTIONS: Shopping trolley. MAIN OUTCOME MEASURES: Changes in lumbar spinal sagittal posture and ground reaction force. RESULTS: Subjects with NC and asymptomatic controls walked with significantly more flexed spinal posture (increase in flexion, 3.40°; z=3.516; P<.001) and reduced mean ground reaction forces (-6.9% of body weight; z=-3.46; P=.001) when walking with a shopping trolley. However, at the midstance point of the gait cycle, controls showed minimal reliance on the trolley, whereas, people with NC showed continued offloading. CONCLUSIONS: Both posture and loading are affected by pushing a shopping trolley; however, patients with NC were found to offload the spine throughout the stance phase of gait, whereas asymptomatic controls did not.

Optimising pain control in osteoarthritis.

A recent large survey showed that 81% of people with osteoarthritis (OA) are in constant pain or are limited in their ability to perform everyday tasks. Patients present with joint pain and stiffness and are often unable to carry out their usual activities which impacts significantly on their quality of life. Anxiety and depression are common in patients with OA and will affect their mood and response to pain so identifying and treating associated anxiety and depression is very important. The PHQ9 and GAD7 can be used to screen for depression and anxiety. The OA process affects all structures within a joint, including the synovial lining and the subchondral bone. When sensitive MRI techniques are used synovitis is found to be almost ubiquitous in painful knee OA. When ultrasound is used, synovitis is seen in up to 45% of patients with painful hand OA. Many current treatments for OA are thought to target the synovium e.g. NSAIDs and this may be why they are effective. Changes in the subchondral bone are also common on MRI and associated with pain. Paracetamol and topical NSAIDs should be tried before oral NSAIDs. Topical NSAIDs are effective in the short-term and are not associated with systemic toxicity. Oral NSAIDs should be used at the lowest effective dose for the shortest possible time. All oral NSAIDs and COX-2 drugs should be prescribed with a PPI. There is less trial data on opioids than on NSAIDs but there is evidence for their efficacy. Patients who have moderate to severe pain that is not responding to oral analgesics or anti-inflammatories may benefit from intra-articular corticosteroids. Timing of analgesia is important. Advise patients to use analgesia before they exercise, so adherence to exercise routines is maintained. Consider long-acting preparations so pain relief is at a maximum throughout the most symptomatic period of the day or night.

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.

Tackling persistent low back pain in primary care.

Non-specific low back pain is pain or discomfort felt in the lower back, where there is no cause identified. It may include symptoms referred to the lower limbs. Those patients who develop chronic pain and disability persisting for more than a year are unlikely to resume normal activities. There is no reliable method of identifying structures responsible for non-specific low back pain. X-rays and MRI are considered to be unhelpful in improving treatment success, and are only recommended for those patients for whom surgery is being considered, or where serious pathology needs to be excluded. Patients should be encouraged to stay active, exercise and carry on with their normal activities. The following approach is recommended initially for persistent low back pain: advice and a stepped approach to analgesics with referral to a pain specialist if longer-term, strong opioids are required. In addition, patients should also be offered up to 12 weeks of one of the following: tailored exercises; manual therapy; or acupuncture. A second option should be offered if the first choice does not provide satisfactory improvement. Combined physical and psychological treatment for up to eight weeks is recommended for patients with severe disability and/or significant psychological distress who have had at least one of the above options.

Improving recognition of psoriatic arthritis.

Psoriatic arthritis (PsA) is a common form of inflammatory arthritis but is underdiagnosed. Psoriasis affects over 1.5% of the UK population. Around 15% of these patients will be diagnosed with PsA, but up to 40% may have evidence of arthritis if reviewed thoroughly. PsA can be difficult to diagnose as patients present with a variety of different patterns of arthritis. Most patients with PsA have relatively mild skin psoriasis, but some have more significant disease. Only 10-20% develop arthritis before their skin disease. Many patients have mild skin psoriasis that they are unaware of, or have not had diagnosed. Joint involvement is far more variable in PsA, compared with rheumatoid arthritis, and patients may present with: monoarthritis; oligoarthritis; involvement of the distal interphalangeal joints; a rheumatoid arthritis-like picture with multiple joints involved including the small joints in the hand or axial disease producing symptoms similar to ankylosing spondylitis. Features such as dactylitis (uniform sausage-like swelling of the whole digit either finger or toe) and enthesitis (inflammation at the sites of muscle or tendon attachment to bone) may also help diagnose PsA. Skin disease is present in the majority of patients although not all. Hidden areas for psoriasis include: behind the ears; at the top of the natal cleft and around the umbilicus. Larger joints, particularly the knees, can develop very big effusions causing obvious swelling. Areas to test for enthesitis should include the Achilles tendon, plantar fascia, costochondral joints and the elbow. Patients with suspected PsA should be referred promptly to a rheumatologist for further assessment and treatment. Diagnosis of PsA can be made on clinical grounds but blood tests and radiographs are performed routinely to aid diagnosis. Initial therapy for PsA should include NSAIDs to ease pain and stiffness. Local injections of corticosteroids are recommended for peripheral arthritis (given IA) and dactylitis (usually by injection into the flexor tendon or adjacent joints). DMARDs are routinely used to treat all aspects of psoriatic disease, except spinal disease, and prescribing should be initiated by a specialist.

Early diagnosis crucial in polyarthralgia.

Polyarthralgia is a common problem with a wide range of differential diagnoses. Clinical assessment is the most important factor in making a diagnosis. History and examination should help to differentiate mechanical from inflammatory disorders, and investigations play a small role. Early intervention, regardless of aetiology, is the key to successful management. Treatment is likely to be a combination of lifestyle modification, physical therapy and medication, and this combined approach is most likely to negate the disability and chronic ill-health traditionally seen in patients with polyarthralgia.

Ultrasound-detected pathologies cluster into groups with different clinical outcomes: data from 3000 community referrals for shoulder pain.

BACKGROUND: Ultrasound is increasingly used to evaluate shoulder pain, but the benefits of this are unclear. In this study, we examined whether ultrasound-defined pathologies have implications for clinical outcomes. METHODS: We extracted reported pathologies from 3000 ultrasound scans of people with shoulder pain referred from primary care. In latent class analysis (LCA), we identified whether individual pathologies clustered in groups. Optimal group number was determined by the minimum Bayesian information criterion. A questionnaire was sent to all patients scanned over a 12-month period (n = 2322). Data collected included demographics, treatments received, current pain and function. The relationship between pathology-defined groups and clinical outcomes was examined. RESULTS: LCA revealed four groups: (1) bursitis with limited inflammation elsewhere (n = 1280), (2) bursitis with extensive inflammation (n = 595), (3) rotator cuff tears (n = 558) and (4) limited pathology (n = 567). A total of 777 subjects (33%) completed questionnaires. The median (IQR) duration post-ultrasound scan was 25 (22-29) months. Subsequent injections were most common in groups 1 and 2 (groups 1-4 76%, 67%, 48% and 61%, respectively); surgery was most common in group 3 (groups 1-4 23%, 21%, 28% and 16%, respectively). Shoulder Pain and Disability Index scores were highest in group 3 (median 48 and 30, respectively) and lowest in group 4 (median 32 and 9, respectively). Patients in group 4 who had surgery reported poor outcomes. CONCLUSIONS: In a community-based population, we identified clusters of pathologies on the basis of ultrasound. Our retrospective data suggest that these groups have different treatment pathways and outcomes. This requires replication in a prospective study to determine the value of a pathology-based classification in people with shoulder pain.

Tofacitinib for treatment of rheumatoid arthritis.

The management of rheumatoid arthritis has seen a dramatic improvement with the introduction of a range of biological disease modifying anti-rheumatic drugs (DMARDs) in recent years. Nonetheless, a proportion of patients remain resistant or intolerant to multiple conventional and biological DMARDs, so innovative strategies are needed to offer patients new therapeutic options. Tofacitinib is the first of a new class of orally active DMARDs, with immunomodulating effects through inhibition of intracellular Janus kinase (JAK) pathways. It has been recently licensed for treatment of adults with moderate to severe RA in the US, Japan, and Russia. In this review the authors evaluate the efficacy and safety of tofacitinib in RA, focusing predominantly on the phase 3 study data.