John Dickson

Care and management of osteoarthritis in adults: summary of NICE guidance

Osteoarthritis refers to a syndrome of joint pain accompanied by functional limitation and reduced quality of life. It is the most common form of arthritis and one of the leading causes of pain and disability in the United Kingdom. The published evidence for osteoarthritis treatment has many limitations—typically, short duration studies using single drug treatments. However, people with osteoarthritis need to be aware of the treatments that represent core management and of the range of additional treatments available. This article summarises the most recent recommendations from the National Institute for Health and Clinical Excellence (NICE) on the care and management of osteoarthritis in adults.1 NICE recommendations are based on systematic reviews of best available evidence. When minimal evidence is available, recommendations are based on the guideline development group’s opinion of what constitutes good practice. Evidence levels for the recommendations are given in italic in square brackets. ### Holistic assessment and management of symptomatic osteoarthritis ### Core treatments Provide advice on the following to all people with symptomatic osteoarthritis:

Cost effectiveness of COX 2 selective inhibitors and traditional NSAIDs alone or in combination with a proton pump inhibitor for people with osteoarthritis

Objectives To investigate the cost effectiveness of cyclo-oxygenase-2 (COX 2) selective inhibitors and traditional non-steroidal anti-inflammatory drugs (NSAIDs), and the addition of proton pump inhibitors to these treatments, for people with osteoarthritis. Design An economic evaluation using a Markov model and data from a systematic review was conducted. Estimates of cardiovascular and gastrointestinal adverse events were based on data from three large randomised controlled trials, and observational data were used for sensitivity analyses. Efficacy benefits from treatment were estimated from a meta-analysis of trials reporting total Western Ontario and McMaster Universities (WOMAC) osteoarthritis index score. Other model inputs were obtained from the relevant literature. The model was run for a hypothetical population of people with osteoarthritis. Subgroup analyses were conducted for people at high risk of gastrointestinal or cardiovascular adverse events. Comparators Licensed COX 2 selective inhibitors (celecoxib and etoricoxib) and traditional NSAIDs (diclofenac, ibuprofen, and naproxen) for which suitable data were available were compared. Paracetamol was also included, as was the possibility of adding a proton pump inhibitor (omeprazole) to each treatment. Main outcome measures The main outcome measure was cost effectiveness, which was based on quality adjusted life years gained. Quality adjusted life year scores were calculated from pooled estimates of efficacy and major adverse events (that is, dyspepsia; symptomatic ulcer; complicated gastrointestinal perforation, ulcer, or bleed; myocardial infarction; stroke; and heart failure). Results Addition of a proton pump inhibitor to both COX 2 selective inhibitors and traditional NSAIDs was highly cost effective for all patient groups considered (incremental cost effectiveness ratio less than £1000 (€1175,

A multicentre, randomized, placebo- and active-controlled trial comparing the efficacy and safety of topical ketoprofen in Transfersome gel (IDEA-033) with ketoprofen-free vehicle (TDT 064) and oral celecoxib for knee pain associated with osteoarthritis

1650)). This finding was robust across a wide range of effectiveness estimates if the cheapest proton pump inhibitor was used. In our base case analysis, adding a proton pump inhibitor to a COX 2 selective inhibitor (used at the lowest licensed dose) was a cost effective option, even for patients at low risk of gastrointestinal adverse events (incremental cost effectiveness ratio approximately £10 000). Uncertainties around relative adverse event rates meant relative cost effectiveness for individual COX 2 selective inhibitors and traditional NSAIDs was difficult to determine. Conclusions Prescribing a proton pump inhibitor for people with osteoarthritis who are taking a traditional NSAID or COX 2 selective inhibitor is cost effective. The cost effectiveness analysis was sensitive to adverse event data and the specific choice of COX 2 selective inhibitor or NSAID agent should, therefore, take into account individual cardiovascular and gastrointestinal risks.

Shoulder acute pain in primary healthcare: is retraining effective for GP principals? SAPPHIRE—a randomized controlled trial

OBJECTIVE To assess the efficacy and safety of 12-week treatment with ketoprofen in ultradeformable phospholipid vesicles in patients with OA knee pain and to compare the efficacy with that of ketoprofen-free vehicle and celecoxib. METHODS; A multicentre, double-blind controlled study in which patients with knee OA and moderate pain were randomized to one of the six arms: topical ketoprofen 50 or 100 mg in ultradeformable vesicles (IDEA-033), 2.2 or 4.4 g ketoprofen-free vehicle (TDT 064), oral celecoxib 100 mg or matching oral placebo, all bd. The primary outcome was change from baseline in the WOMAC pain subscale at week 12. RESULTS A total of 1395 patients received treatment. Baseline mean WOMAC pain scores ranged from 4.7 to 4.8 across groups. The mean reduction in WOMAC pain score at week 12 was -1.9 (-40.8%) for ketoprofen 50 mg, -1.9 (-40.9%) for ketoprofen 100 mg, -1.9 (-39.8%) for 2.2 g TDT 064, -1.8 (-37.8%) for 4.4 g TDT 064, -1.9 (-40.4%) for celecoxib and -1.4 (-29.3%) for oral placebo. IDEA-033 was not statistically superior to TDT 064. All topical treatments were statistically superior to oral placebo and non-inferior to celecoxib. The most frequent types of treatment-related adverse events reported were gastrointestinal for oral (15.9% for celecoxib) and dermal for topical applications (12.2% for ketoprofen 100 mg). CONCLUSION IDEA-033 was not superior to ketoprofen-free vehicle, but both formulations were superior to oral placebo and non-inferior to celecoxib in reducing OA knee pain. TRIAL REGISTRATION ClinicalTrials.gov, http://clinicaltrials.gov/, NCT00716547.

Hydroxychloroquine effectiveness in reducing symptoms of hand osteoarthritis (HERO): study protocol for a randomized controlled trial.

OBJECTIVE To address the question whether general practitioners (GPs) should receive practical training in shoulder problems and to test whether cortisone injections are better than anaesthetic injections for rotator cuff problems. METHODS A pragmatic split-plot, randomized trial with a cluster factorial design, conducted in general practices across five centres across the United Kingdom. Ninety-one practices were randomized to receive additional training in diagnosing and injecting rotator cuff problems or no additional training. Two hundred patients consulting their general practices with shoulder pain were then randomized to receive either a corticosteroid or lignocaine injection. The main outcome was score on the British Shoulder Disability Questionnaire (BSDQ). The Short-Form 36-item Health Survey and EuroQol at 12 months from entry to the trial were also scored. RESULTS Over the course of the trial there was a mean difference of 0.94 (s.e. = 1.01) on the BSDQ score between the groups, with patients treated by the untrained group having a mean of 9.46 (s.e. = 0.82) and those by the trained group having a mean of 8.51 (s.e. = 0.60). There were no statistically significant differences between the groups. Analysing by substance injected, there was a mean difference of 0.15 (s.e. = 0.48) throughout the trial between the groups, with patients given the cortisone having a mean BSDQ of 9.67 (s.e. = 0.39) and those given lignocaine, 9.82 (s.e. = 0.39). This was not statistically significantly different. CONCLUSIONS Training GPs in the diagnosis and treatment of shoulder disorders does not make any difference to the outcome, in terms of pain and disability, 1 yr later. Further, there is no advantage to injecting steroid in a group with predominant rotator cuff disorder. Trial registration. International Standard Randomized Controlled Trial Number 58537244. Trial steering committee comprised Prof. Paul Dieppe, Prof. Elaine Hay, Dr Brian Hazleman and Dr Kerenza Hood.

Shoulder acute pain in primary health care: is retraining GPs effective? The SAPPHIRE randomized trial: a cost–effectiveness analysis

BackgroundOsteoarthritis (OA) is the most common type of arthritis, causing significant joint pain and disability. It is already a major cause of healthcare expenditure and its incidence will further increase with the ageing population. Current treatments for OA have major limitations and new analgesic treatments are needed. Synovitis is prevalent in OA and is associated with pain. Hydroxychloroquine is used in routine practice for treating synovitis in inflammatory arthritides, such as rheumatoid arthritis. We propose that treating patients with symptomatic hand OA with hydroxychloroquine will be a practical and safe treatment to reduce synovitis and pain.Methods/designHERO is an investigator-initiated, multicentre, randomized, double-blind, placebo-controlled trial. A total of 252 subjects with symptomatic hand OA will be recruited across primary and secondary care sites in the UK and randomized on a 1:1 basis to active treatment or placebo for 12 months. Daily medication dose will range from 200 to 400 mg according to ideal body weight. The primary endpoint is change in average hand pain during the previous two weeks (measured on a numerical rating scale (NRS)) between baseline and six months. Secondary endpoints include other self-reported pain, function and quality-of-life measures and radiographic structural change at 12 months. A health economics analysis will also be performed. An ultrasound substudy will be conducted to examine baseline levels of synovitis. Linear and logistic regression will be used to compare changes between groups using univariable and multivariable modelling analyses. All analyses will be conducted on an intention-to-treat basis.DiscussionThe HERO trial is designed to examine whether hydroxychloroquine is an effective analgesic treatment for OA and whether it provides any long-term structural benefit. The ultrasound substudy will address whether baseline synovitis is a predictor of therapeutic response. This will potentially provide a new treatment for OA, which could be of particular use in the primary care setting.Trial registrationISRCTN91859104.

Value of information in the osteoarthritis setting: cost effectiveness of COX-2 selective inhibitors, traditional NSAIDs and proton pump inhibitors

OBJECTIVES To assess the cost-effectiveness of providing practical training to general practitioners (GPs) in shoulder problems, and administering a local anaesthetic (lignocaine) vs steroidal (cortisone) injection. METHODS A cost-effectiveness analysis conducted alongside a cluster randomized trial with a factorial design, in general practices across five centres within the UK. A total of 155 participant GPs were randomized to receive training or no training with 200 participants randomized to either lignocaine or cortisone. Health care costs, quality-adjusted life years (QALYs) and incremental cost per QALY gained over 1 year estimated from a health system and a societal perspective were the main outcomes measured. RESULTS Over 1 year, training GPs costs on average an additional pound sterling 211 (95% credibility interval - pound sterling 237, pound sterling 661) than no training and produces higher mean QALYs (0.075; -0.004, 0.154) per patient, yielding an incremental cost-effectiveness ratio of pound sterling 2813 per QALY gained for trained GPs. Over the same period of 1 year, lignocaine costs an average of pound sterling 122 more (- pound sterling 232, pound sterling 476) than cortisone and produces virtually no differential gain in mean QALYs (0.001; -0.068, 0.070), yielding an incremental cost per QALY gained of pound sterling 122,000 for lignocaine compared with cortisone. Across a range of cost-effectiveness thresholds, cortisone is as cost effective to inject as lignocaine. The probability that training is cost effective is above 0.95 at thresholds above pound sterling 20,000. CONCLUSIONS Providing practical training to GPs about shoulder problems is cost effective and there is little uncertainty regarding this decision. The choice between lignocaine and cortisone is more uncertain and it is likely that there is significant value of further research to reduce this uncertainty. TRIAL REGISTRATION The International Standard Randomised Controlled Trial Number is 58 537 244.

Managing osteoarthritis in primary care

AbstractBackground: Recent National Institute for Health and Clinical Excellence (NICE) guidance recommended that when traditional NSAIDs or cyclooxygenase (COX)-2 selective inhibitors are used by people with osteoarthritis (OA), they should be prescribed along with a proton pump inhibitor (PPI). However, specific recommendations about the type ofNSAID orCOX-2 could not be made due to high levels of uncertainty in the economic evaluation. Objective: To investigate the value of obtaining further evidence to inform the economic evaluation of NSAIDs, COX-2s and PPIs for people with OA. Methods: An economic evaluation with an expected value of perfect information (EVPI) analysis was conducted, using a Markov model with data identified from a systematic review. The base-case model used adverse event data from the three largest randomized trials of COX-2 inhibitors, and we repeated the analysis using observational adverse event data. The model was run for a hypothetical population of people with OA, and subgroup analyses were conducted for people with raised gastrointestinal (GI) and cardiovascular (CV) risk. The EVPI was based upon the OA population in England — approximately 2.8 million people. Of these, 50% were assumed to use NSAIDs or COX-2 selective inhibitors for 3 months per year and 56% of these were assumed to be patients with raised GI and CV risk. Results: The value of further information for this decision problem was very high. Population-level EVPI was £85.1 million in the low-risk group and £179.5 million in the high-risk group (2007–8 values). Expected value of partial perfect information (EVPPI) analysis showed that the groups of parameters for which further evidence was likely to be of most value were CV adverse event risks and all adverse event rates associated with the specific drugs celecoxib and ibuprofen. The value of perfect information remained high even when observational adverse event data were used. Conclusions: There is a very high value associated with obtaining further information on uncertain parameters for the economic evaluation of NSAIDs, COX-2 selective inhibitors and PPIs for people with OA. Obtaining further randomized or observational information on CV risks is likely to be particularly cost effective.

Evidence-based recommendations for the role of exercise in the management of osteoarthritis of the hip or knee—the MOVE consensus

Introduction. Osteoarthritis Aetiology and Epidemiology. Diagnosis and Differential Diagnosis of Osteoarthritis. Examination of Joints. Assessment of Osteoarthritis. Assessment of Hand Osteoarthritis. Management Options -- Education and Behavioural and Environmental. Physical Therapy and Mechanical Interventions. Pharmacological Treatment. Surgical Options and Procedures. Long Term Management and Referral. Economic and Research Considerations. . Appendices:. GALS Screening Examination. WOMAC and Lequesne scales. Beighton score. Useful addresses. Useful websites