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and exercise). The primary outcome measure was hip-related quality of life using the patient-reported International Hip Outcome Tool (iHOT-33) at 12 months (score 0-100, higher scores indicate better quality of life, and the minimal clinical important difference is 6.1). Secondary outcomes included generic health-related quality of life (EQ5D5L, SF12), adverse events, and cost-effectiveness. Primary analysis compared the differences in iHOT-33 scores at 12 months between groups, by intention to treat. Cost-effectiveness analysis took an NHS and personal social services perspective. Results: Of 6028 patients attending hip clinics at participating sites, 648 patients were eligible and 348 were randomised (171 to HA; 177 to PHT). There were no important differences between the groups in baseline characteristics. The average time to surgery was 132 days (SD 71) versus 47 days (SD 52) to PHT. 92.5% were followed-up for the primary outcome at 12 months. Baseline mean and standard deviation in iHOT-33 scores were 39.2 (SD 21) and 35.6 (SD 18) in the surgery and PHT groups, and 58.8 (SD 27) and 49.7 (SD 25) at 12 months, respectively. On average, patients in both groups improved over 12 months, and the mean iHOT-33 score increased more in those allocated to HA than to PHT, with a mean difference of 6.8 points (95% CI 1.7,12.0 p ¼ 0.009) in favour of surgery. Muscle soreness was common in both groups; one HA patient developed an infection requiring further surgery. Mean overall costs were £3713 for HA and £1283 for PHT. Conclusions: Treatment of patients with FAI syndrome with a strategy of either physiotherapy-led best conservative care or arthroscopic hip surgery led to improved hip-related quality of life. At 12 month followup that improvement was significantly greater in those allocated to surgery than in those allocated to conservative care. Hip arthroscopy was safe, but is associated with higher overall cost than conservative care over 12 months.

Purpose: Most drug treatments for osteoarthritis (OA) do not achieve a minimum clinically important difference above placebo and often associate with side-effects. On average, 75% of the analgesic effect from OA treatments in clinical trials, and potentially in clinical practice, can be attributed to placebo/contextual response, though the magnitude of this response may vary greatly between patients. We undertook this individual patient data (IPD) meta-analysis of three contrasting treatments for OA to identify placebo responders and the potential determinants of the placebo response in OA. Methods: This study is undertaken in conjunction with the OA Trial Bank, an ongoing international consortium collecting IPD from randomised controlled trials (RCTs) for treatments of OA. Placebo-controlled RCTs for intra-articular (IA) corticosteroid injections, oral glucosamine tablets, and topical non-steroidal anti-inflammatory drugs (NSAID) have been systematically searched for and authors contacted to request the IPD. Outcomes The primary outcome measure for placebo response was maximum pain reduction over the duration of follow-up (1-119 weeks). Potential predictors and covariates available were intervention type, radiographic Kellgren and Lawrence (KL) score, sex, age, body mass index (BMI), duration of OA (years) and study joint. Data Analysis Pain was measured using different scales across trials and was normalised into a 0-100 scale for analysis. Maximum pain reduction was identified for each participant. Participants who achieved clinically important pain relief, defined as 20% reduction in pain score from baseline, were classified as responders. A one-stage IPD meta-analysis was used to analyse all studies simultaneously whilst accounting for heterogeneity across studies. A multilevel mixed-effects linear regression model was fitted. Maximum change from baseline pain score was the dependent variable, whereas baseline pain, age, sex, BMI and other potential predictors were independent variables. Univariate analysis was used to select significant predictors. Significant predictors were then examined in a multivariate model to confirm the results. Results: Characteristics of study population Eighteen out of 19 identified trials provided IPD for this analysis. Data on 2,305 placebo participants were available for analysis. Of these studies, 4 trials (n¼674 participants) used placebo tablets, 3 trials (n¼78) used IA placebo injection and 11 trials (n¼1,553) used topical placebo. Thirteen studies (n¼1,764) included participants with knee OA, three (n¼158) included participants with hip OA, and two (n¼383) included participants with hand OA. Placebo response 75% of participants reported 20% pain reduction from baseline. The mean age was 61.94 years (95% CI 61.45 to 62.43) for responders and 61.85 (95% CI 61.00 to 62.70) for non-responders. The response rate in females was 75% and males 75%. The mean BMI was 30.05 (95% CI 29.73 to 30.38) for responders and 29.69 (95% CI 29.18 to 30.20) for non-responders. Absolute pain red...

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BackgroundInflammation of the synovium and in particular the bone marrow, as assessed by magnetic resonance imaging (MRI), have been identified as prognostic indicators of structural joint damage in patients (pts) with rheumatoid arthritis (RA). Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. Inhibition of structural damage has been shown using conventional radiography in pts receiving tofacitinib for moderate to severe RA.1,2ObjectivesTo explore the effects of tofacitinib, with or without methotrexate (MTX), on a range of sensitive MRI endpoints.MethodsThis was an exploratory, Phase 2, randomised, double-blind, parallel group, multicentre study (A3921068; NCT01164579) in MTX-naive adults with early active RA (duration ≤2 years) and evidence of clinical synovitis in an index wrist or metacarpophalangeal (MCP) joint. Pts were randomised 1:1:1 to receive tofacitinib 10 mg twice daily (BID) + MTX, tofacitinib 10 mg BID + placebo (PBO) or MTX + PBO, for 1 year. MRI endpoints in the wrist and MCP joints were assessed using 3 methods: OMERACT RAMRIS; a novel automated method quantifying RAMRIS components using Active Appearance Modelling (RAMRIQ; Imorphics UK); and dynamic quantitative MRI (Dynamika, UK). Evaluable pts were assessed using a mixed effect model for repeated measures to evaluate endpoints (statistical significance at 10% [2-sided] level). Scoring was performed by one centralised reader blinded to time point and treatment.ResultsOf 109 pts randomised and treated, most were female and Caucasian. Disease duration was consistent with early RA (mean: 0.6–0.8 years). Mean age, disease activity and MRI evaluations were similar across treatment groups at baseline (BL). More pts from the tofacitinib + MTX and tofacitinib + PBO groups completed the study (n=28, n=27, respectively) vs MTX + PBO (n=21). Mean BME improvements, measured with RAMRIS and RAMRIQ only, were statistically greater in both tofacitinib groups vs MTX + PBO at M3, M6 (primary; RAMRIS) and M12. Synovitis improvements were observed in all groups; numerical improvements were observed in both tofacitinib groups vs MTX + PBO with RAMRIS, but statistically significant differences were observed for both tofacitinib groups across time points with the more sensitive RAMRIQ, which was consistent with dynamic MRI findings (Table 1). Significantly less erosive damage was seen using RAMRIS and RAMRIQ in both tofacitinib groups vs MTX + PBO at M6 and M12 (Table 1).ConclusionsThese results provide consistent evidence using 3 different MRI assessment technologies that tofacitinib treatment leads to early reduction of inflammation and lack of progression of structural damage.ReferencesLee EB et al. N Engl J Med 2014; 370:2377-86. 2. van der Heijde, et al. Arthritis Rheum 2013; 65:559-70.AcknowledgementsRAMRIS data presented previously (Conaghan P, et al. Arthritis Rheum 2014; 66 (11): S375 abs 849) and reproduced with permission from Arthritis and Rheumatism. All aspects of this study were funded by Pfizer Inc. Editorial support was provide...