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Background The objective of this study was to evaluate early changes in magnetic resonance imaging (MRI) and clinical disease activity measures as predictors of later structural progression in early rheumatoid arthritis (RA). Methods This was a post hoc analysis of data pooled across treatments from a three-arm (tofacitinib monotherapy, tofacitinib with methotrexate [MTX], or MTX monotherapy) trial of MTX-naïve patients with early, active RA. Synovitis, osteitis and erosions were assessed with the Outcome Measures in Rheumatology (OMERACT) RA MRI scoring system (RAMRIS) and RAMRIQ (automated quantitative RA MRI assessment system; automated RAMRIS) at months 0, 1, 3, 6 and 12. Radiographs were assessed at months 0, 6 and 12, and clinical endpoints were assessed at all timepoints. Univariate and multivariate analyses explored the predictive value of early changes in RAMRIS/RAMRIQ parameters and disease activity measures, with respect to subsequent radiographic progression. Results Data from 109 patients with a mean RA duration of 0.7 years were included. In univariate analyses, changes in RAMRIS erosions at months 1 and 3 significantly predicted radiographic progression at month 12 (both p p p p Conclusions MRI changes seen as early as 1 month after RA treatment initiation have the potential to better predict long-term radiographic progression than changes in disease activity measures. Trial registration ClinicalTrials.gov, NCT01164579.

Background:Magnetic resonance imaging (MRI) trial outcomes have largely focused on synovitis, bone marrow oedema (BME) and erosions. Tenosynovitis is a common manifestation of rheumatoid arthritis (RA), but is relatively understudied; a combined inflammation score (CIS) summing synovitis, BME and tenosynovitis may be a highly responsive measure. We previously showed the responsiveness of the Outcome Measures in Rheumatology (OMERACT) RA MRI scoring system (RAMRIS) and a machine-learning derived automated tool (RAMRIQ) in a randomised controlled trial (RCT) of tofacitinib and methotrexate (MTX) in MTX-naïve patients (pts) with early RA.1Objectives:This post hoc analysis assessed the impact of tofacitinib ± MTX on MRI tenosynovitis and CIS in pts with early RA using semiquantitative and quantitative MRI outcomes.Methods:Study A3921068 (NCT01164579), a 1-year, exploratory, Phase 2, RCT, compared tofacitinib 10 mg twice daily (BID) ± MTX, and MTX monotherapy, in MTX-naïve pts with early RA.1 MRI of unilateral wrist and metacarpophalangeal joints was performed at screening/baseline (BL) and Months (M)1/3/6/12. MRI tenosynovitis and CIS were assessed using RAMRIS and RAMRIQ. Changes from BL (Δ) in RAMRIS and RAMRIQ tenosynovitis and CIS were evaluated at M1/3/6/12. Data were assessed using a mixed-effect model for repeated measures, with treatment arms as factors and BL values as covariates. Using data pooled across treatment arms, Spearman’s rank correlation coefficients were calculated for associations between BL RAMRIS and BL RAMRIQ tenosynovitis and CIS vs BL Disease Activity Score in 28 joints, C-reactive protein (DAS28-4[CRP]), and ΔRAMRIS and ΔRAMRIQ tenosynovitis and CIS at M12 vs ΔDAS28-4(CRP) at M12.Results:In total, 109 pts were randomised and treated. ΔRAMRIS and ΔRAMRIQ tenosynovitis and CIS were generally significantly greater at M3/6/12 in pts receiving tofacitinib ± MTX vs MTX, while ΔRAMRIQ CIS was also significantly greater at M1 (Figure 1). Compared with RAMRIS, RAMRIQ outcomes were generally more responsive to treatment with tofacitinib ± MTX. Significant correlations were seen between BL RAMRIS and BL RAMRIQ tenosynovitis and BL RAMRIS CIS vs BL DAS28-4(CRP), and between ΔRAMRIS and ΔRAMRIQ tenosynovitis and CIS at M12 vs ΔDAS28-4(CRP) at M12 (Table 1). In general, stronger correlations were seen between BL DAS28-4(CRP) and BL RAMRIS vs BL RAMRIQ parameters, while correlations were similar between ΔDAS28-4(CRP) at M12 and ΔRAMRIS and ΔRAMRIQ parameters at M12.Table 1.Correlations between a) BL RAMRIS and BL RAMRIQ tenosynovitis and CIS vs BL DAS28-4(CRP) (N=109) and b) ΔRAMRIS and ΔRAMRIQ tenosynovitis and CIS at M12 vs ΔDAS28-4(CRP) at M12 (N=73) across treatment armsaa)BL DAS28-4(CRP)b)ΔDAS28-4(CRP)BL imaging featureCorrelationp valueΔImaging featureCorrelationp valueRAMRIStenosynovitis0.3660.0001RAMRIStenosynovitis0.531RAMRIS CIS0.399RAMRIS CIS0.554RAMRIQtenosynovitis0.2050.037RAMRIQtenosynovitis0.543RAMRIQ CIS0.1800.062RAMRIQ CIS0.564aData were pooled across the tofacitinib 10 mg BID ± MTX and MTX monotherapy armsSpearman’s rank correlation coefficients and p values were calculated for associations between RAMRIS and RAMRIQ parameters and DAS28-4(CRP); tenosynovitis and CIS were assessed using combined data from metacarpophalangeal and wrist joints; CIS is the sum of synovitis, BME and tenosynovitis valuesΔ, change from BL; N, number of pts with values at BL/timepoint of interestConclusion:Responsiveness of RAMRIS and RAMRIQ tenosynovitis and CIS was demonstrated with significant improvements through M12 in pts receiving tofacitinib 10 mg BID ± MTX vs MTX. Construct validity for RAMRIS and RAMRIQ tenosynovitis and CIS was evident from correlations with DAS28-4(CRP). Further work is needed to validate these novel imaging biomarkers in terms of relative responsiveness and prediction of later structural progression.References:[1]Conaghan et al. Ann Rheum Dis 2016; 75: 1024-1033.Acknowledgements:Study sponsored by Pfizer Inc. Medical writing support was provided by Jennifer Arnold, CMC Connect, and funded by Pfizer Inc.Disclosure of Interests:Philip G Conaghan Speakers bureau: AbbVie, Novartis, Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, Flexion, Galapagos, Gilead Sciences, GlaxoSmithKline, Janssen, Novartis, Pfizer Inc, Regeneron, Mikkel Østergaard Speakers bureau: AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Eli Lilly, GlaxoSmithKline, Hospira, Janssen, Merck, Mundipharma, Novartis, Novo, Orion, Pfizer Inc, Regeneron, Roche, Schering-Plough, Takeda, UCB, Wyeth, Consultant of: AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Eli Lilly, GlaxoSmithKline, Hospira, Janssen, Merck, Mundipharma, Novartis, Novo, Orion, Pfizer Inc, Regeneron, Roche, Schering-Plough, Takeda, UCB, Wyeth, Grant/research support from: AbbVie, Centocor, Merck, Orrin Troum Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Horizon, Novartis, Pfizer Inc, Sanofi-Genzyme, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Horizon, Pfizer Inc, Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Centocor, Corrona, Novartis, Pfizer Inc, Zhiyong Xie Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Alan Brett Shareholder of: Stryker Corp, Employee of: Stryker Corp, Mark Snyder Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Abbas Ebrahim Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Douglass Chapman Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Gosford Sawyerr Consultant of: Pfizer Inc, Employee of: Syneos Health, John Andrews Shareholder of: Pfizer Inc, Employee of: Pfizer Inc

ObjectiveIn rheumatoid arthritis (RA), MRI provides earlier detection of structural damage than radiography (X-ray) and more sensitive detection of intra-articular inflammation than clinical examination. This analysis was designed to evaluate the ability of early MRI findings to predict subsequent structural damage by X-ray.MethodsPooled data from four randomised controlled trials (RCTs) involving 1022 RA hands and wrists in early and established RA were analysed. X-rays were scored using van der Heijde-modified or Genant-modified Sharp methods. MRIs were scored using Outcome Measures in Rheumatology (OMERACT) RA MRI Score (RAMRIS). Data were analysed at the patient level using multivariable logistic regression and receiver operating characteristic curve analyses.ResultsProgression of MRI erosion scores at Weeks 12 and 24 predicted progression of X-ray erosions at Weeks 24 and 52, with areas under the curve (AUCs) of 0.64 and 0.74, respectively. 12-week and 24-week changes in MRI osteitis scores were similarly predictive of 24-week and 52-week X-ray erosion progressions; pooled AUCs were 0.78 and 0.77, respectively. MRI changes in synovitis at Weeks 12 and 24 also predicted progression of X-ray joint damage (erosion and joint-space narrowing) at Weeks 24 and 52 (AUCs=0.72 and 0.65, respectively).ConclusionsEarly changes in joint damage and inflammation detected with MRI predict changes in joint damage evident on subsequent X-rays. These findings support the use of MRI as a valid method for monitoring structural damage in short-duration RCTs.

Objective To determine the characteristics and response to pegloticase of patients with chronic refractory gout with and without clinically apparent tophi. Methods Results from two randomized controlled trials of pegloticase in patients with chronic refractory gout with clinically apparent tophi or without tophi were used to assess baseline and on-treatment between-group differences. Results Patients with tophi were significantly older than those without tophi, had a significantly longer duration of disease, higher numbers of tender and swollen joints, higher Patient Global Assessment scores and Health Assessment Questionnaire-Disability Index scores, and lower Arthritis-Specific Health Index scores. Patients with tophaceous gout also had significantly lower scores for physical functioning, role physical, social functioning, and the physical component summary scores of the Short Form 36 vs patients without tophi. In addition, subjects with clinically apparent tophi had a significantly lower mean estimated glomerular filtration rate. Pegloticase treatment of tophaceous patients caused significant reductions in serum urate, flares, Patient Global Assessment, tender joints, swollen joints, Health Assessment Questionnaire-Disability Index, visual analogue scale pain and Short Form 36 Bodily Pain, whereas patients without tophi had significant improvement in serum urate, flares, Patient Global Assessment, tender joints, and Short Form 36 Bodily Pain, but not swollen joints, Health Assessment Questionnaire-Disability Index functional score or pain visual analogue scale. Treatment with pegloticase had no effect on estimated glomerular filtration rate despite significant lowering of the urinary uric acid: creatinine ratio. Conclusion Patients with chronic refractory gout and clinically apparent tophi have more severe disease as well as reduced renal function. Both groups experienced significant clinical benefit with pegloticase treatment, although no change in renal function was noted.

Background Many, but not all patients with chronic refractory gout develop tophi; and the factors that govern tophus formation are not known. To address this question, we assessed subjects enrolled in the pivotal trials of pegloticase, a mammalian recombinant uricase conjugated to polyethylene glycol that is approved for the treatment of gout refractory to conventional oral urate lowering therapy. Objectives To determine the factors associated with the presence of tophi in patients with chronic refractory gout. Methods This analysis used results from two pivotal randomised controlled trials (RCTs)1,2 to assess the clinical characteristics of subjects with chronic refractory gout and effects of treatment with pegloticase. Overall, 73% of the subjects in these trials had clinically apparent tophi at baseline and 27% did not. Demographic features of these subjects were assessed and renal function was evaluated by measurement of estimated glomerular filtration rate (eGFR). Subjects were treated with pegloticase, 8 mg every other week (q2w) in a 6 month RCT and then followed for up to 3 years in an open label extension (OLE). Results The analysis included subjects with chronic refractory gout, 154 with tophi at baseline and 57 without tophi. Chronic refractory gout subjects in the two groups were generally similar at baseline, but with a difference in disease duration: 16.3 years for tophaceous subjects vs 11.7 years for subjects without tophi (p=0.007). There were no significant differences in most comorbidities for the two groups. However, eGFR was significantly lower in the subjects with tophi (85.2 mL/min) vs those without tophi (116.5 mL/min) (p=0.001). The frequency of tophi increased in subjects with lower eGFR values (Table). Six months of treatment with pegloticase (8 mg q2w) in a subgroup of subjects resulted in complete or partial resolution of at least one tophus with no increase in others in 74% of subjects, but had no significant effect on renal function measured by eGFR (78.8 mL/min vs 84.2 mL/min, n=51, p=0.7). Continued treatment with pegloticase in the OLE further decreased the burden of tophi, but had no significant effect on renal function measured by eGFR (75.7 mL/min, p=0.6). Conclusions These results indicate that chronic refractory gout patients may present with or without clinically apparent tophi. A significant association was noted between the presence of renal dysfunction measured by eGFR and the frequency with which chronic refractory gout patients manifested tophi. Pegloticase treatment markedly decreased the tophus burden, but in this analysis did not improve renal function. These results suggest that renal failure may predispose patients to tophus formation, whereas the resolution of tophi in this analysis did not appear to improve renal function. References [1] Sundy JS, Baraf HS, Yood RA, et al. JAMA2011;306:711–720. [2] Baraf HS, Becker MA, Gutierrez-Urena SR, et al. Arthritis Res Ther2013;15:R137. Disclosure of Interest N. L. Edwards Consultant for: AstraZeneca, Horizon Pharma, Ironwood Pharmaceuticals, SOBI International, J. Singh: None declared, O. Troum Shareholder of: Theralogix, Grant/research support from: Abbvie, Amgen, CORONA, Novartis, Pfizer, R-Pharm, Consultant for: Abbvie, Amgen, BMS, Pfizer, Roche, Genentech, Speakers bureau: Abbvie, Amgen, BMS, Celgene, Novartis, Pfizer, Roche, Genentech, A. Yeo Consultant for: Horizon Pharma, P. Lipsky Consultant for: Horizon Pharma

Background The term “chronic refractory gout” defines a subset of chronic gout patients who are either intolerant of or unresponsive to standard uric acid (UA) lowering therapy (ULT). Subjects (N=85) meeting this definition were enrolled in a study of pegloticase (8 mg every 2 weeks [q2w], the approved dose), a mammalian recombinant uricase conjugated to polyethylene glycol that is approved for the treatment of gout refractory to conventional oral ULT. Of this group of subjects, 73% had clinically apparent tophi, whereas 27% did not. Objectives To determine the clinical characteristics and response to pegloticase therapy in patients with chronic refractory gout with and without clinically apparent tophi. Methods This analysis used results from two pivotal randomized controlled trials 1 to assess the clinical characteristics and the efficacy of pegloticase (8 mg q2w) in patients with chronic refractory gout with or without tophi at baseline. The results for serum urate (UA), flares, Patient Global Assessment (PGA), tender and swollen joints (TJC and SJC), bodily pain, Health Assessment Questionnaire-Disability Index (HAQ-DI), and the Arthritis-Specific Health Index (ASHI) and Bodily Pain from the Medical Outcomes Study Short Form 36 item (SF-36) were determined for each group. Results The analysis included patients with chronic refractory gout, 62 with tophi at baseline and 23 without tophi. Chronic refractory gout patients in the two groups were similar at baseline, with the only significant differences in mean values between tophaceous and nontophaceous gout groups as follows: TJC, 14.2 vs 5.00 (P=0.01); SJC, 10.9 vs 3.4 (P=0.003); ASHI, 50.4 vs 64.7 (P=0.03); and HAQ-DI, 1.3 vs 0.6, respectively (P=0.001). Other measures of disease impact and comorbidities were not significantly different between groups. Treatment with pegloticase 8 mg q2w resulted in significant and comparable reductions in serum UA in both groups. Comparison of results from baseline and after 6 months of treatment for patients with tophi at baseline indicated significant reductions in serum UA (P Conclusions These results indicate that chronic refractory gout patients may present with or without clinically apparent tophi. Tophaceous patients are distinguished by more tender and swollen joints, greater disability, and greater arthritis severity, but otherwise are similar to nontophaceous patients. Both groups had significant clinical benefit over 6 months of treatment with pegloticase. References Sundy JS, Baraf HS, Yood RA, et al. JAMA. 2011;306:711–720. Baraf HS, Becker MA, Gutierrez-Urena SR, et al. Arthritis Res Ther. 2013;15:R137. Disclosure of Interest N. L. Edwards Consultant for: AstraZeneca, Horizon Pharma, Ironwood Pharmaceuticals, SOBI International, J. Singh: None declared, O. Troum Shareholder of: Theralogix, Grant/research support from: Abbvie, Amgen, CORONA, Novartis, Pfizer, R-Pharm, Consultant for: Abbvie, Amgen, BMS, Pfizer, Roche, Genentech, Speakers bureau: Abbvie, Amgen, BMS, Celgene, Novartis, Pfizer, Roche, Genentech, A. Yeo Consultant for: Horizon Pharma, P. Lipsky Consultant for: AstraZeneca, Celgene, EMD Serono, GSK, Horizon Pharma, Janssen, Medimmune, Pfizer, Roche, Sanofi, UCB

Advances in rheumatology occur at a rapid pace and staying abreast of important changes is a challenge for all. Both novel drug development and enhanced understanding of conventional or historic therapies have molded current day rheumatologic practice. Rheumatology has led the way in the use of outcome measures and imaging modalities in common disorders like rheumatoid arthritis, osteoarthritis, and gout. The expertise of the rheumatologist has widened such that knowledge of economics, legal issues, related disorders and extraarticular disease is essential. In February 2013, the 6th annual Rheumatology Winter Clinical Symposium was held. At this meeting, faculty and participants held discussions and exchanged knowledge about new scientific data and how it may impact the care of rheumatology patients. Excerpts from some of the lectures from the Rheumatology Winter Clinical Symposium 2013 are included in this review. These and other presentations can be viewed in their entirety at http://www.r-w-c-s.com.

Early diagnosis and treatment have been recognized as essential for improving clinical outcomes in patients with rheumatoid arthritis (RA). Magnetic resonance imaging (MRI) is a sensitive modality that can assess both inflammatory and structural lesions. MRI can assist in following the disease course in patients treated with traditional disease-modifying antirheumatic drugs and biological therapies both in the clinic and in research trials. Therefore, it is anticipated that MRI becomes the diagnostic imaging modality of choice in RA clinical trials while remaining a useful tool for clinicians evaluating patients with RA.

saw my first patient with rheumatoid arthritis (RA) when Iwas 12 years old. My father, Nathan Troum, was also arheumatologist, and I would join him when he saw patients inhis office. At that time, in 1964, the typical treatmentsavailable for patients with RA were intramuscular gold,high-dose aspirin, and corticosteroids—indomethacin wasjust introduced.Inthe1980s,methotrexatewasapprovedforRAand,inmore recent years, biologic response-modifying agents haveadded significantly to our armamentarium. It was then thatrheumatologists realized that we needed better tools to helpdetect early damage. Such tools would enable us to use moreeffective medications in an attempt to prevent damage early.That was the pretext for my getting involved with office-based magnetic resonance imaging (MRI).

The International Society for Musculoskeletal Imaging in Rheumatology (ISEMIR) was founded in 2005 with the goal of discussing matters related to imaging in rheumatology, particularly, validation, education, and use in both clinical practice and research. The field of musculoskeletal (MSK) imaging is continuously evolving; therefore, education for healthcare providers in this field is of paramount importance. ISEMIR's international faculty and world-renowned experts presented the newest information as it relates to the use of magnetic resonance imaging (MRI) and ultrasound (US) at the 8th annual ISEMIR meeting that took place on April 17-18 in Santa Monica, California. Presentations from the meeting can be viewed at www.isemir.org.

Hip pain in young adults (18-35 years old) often is characterized by nonspecific symptoms, normal imaging studies, and vague findings from the history and physical examination. In younger patients, pain is more likely to be caused by congenital hip dysplasia, athletic injuries, trauma, spondyloarthropathy, and by conditions that first appear during this stage of life, such as rheumatoid arthritis, osteoarthritis, intravenous drug use, alcoholism, or corticosteroid use. The history and physical examination may narrow the diagnosis to intraarticular, extraarticular, or referred sources of pain. Plain radiography and magnetic resonance imaging are the preferred initial imaging procedures. Analyses of the blood, urine, and synovial fluid can be helpful in diagnosing inflammation, infection, and systematic rheumatic disease. Fractures, infection, and ischemic necrosis should be ruled out early because they require immediate treatment to prevent damage to the joint. Hip trauma at a young age increases the risk of osteoarthritis with advancing age, and, unlike most older adults, young adults receiving total hip replacement can expect revision surgery. Medical treatment often involves patient education, physical therapy, and pharmacotherapy. Acetaminophen, nonsteroidal anti-inflammatory drugs, and opioids for pain and antibiotics for infection are the most often prescribed drugs for this population.

ObjectiveTo assess the efficacy and safety of tocilizumab (TCZ) plus methotrexate/placebo (MTX/PBO) over 2 years and the course of disease activity in patients who discontinued TCZ due to sustained remission.MethodsACT-RAY was a double-blind 3-year trial. Patients with active rheumatoid arthritis despite MTX were randomised to add TCZ to ongoing MTX (add-on strategy) or switch to TCZ plus PBO (switch strategy). Using a treat-to-target approach, open-label conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), other than MTX, were added from week 24 if Disease Activity Score in 28 joints based on erythrocyte sedimentation rate (DAS28-ESR) >3.2. Between weeks 52 and 104, patients in sustained clinical remission (DAS28-ESR ResultsOf the 556 randomised patients, 76% completed year 2. Of patients entering year 2, 50.4% discontinued TCZ after achieving sustained remission and 5.9% achieved drug-free remission. Most patients who discontinued TCZ (84.0%) had a subsequent flare, but responded well to TCZ reintroduction. Despite many patients temporarily stopping TCZ, radiographic progression was minimal, with differences favouring add-on treatment. Rates of serious adverse events and serious infections per 100 patient-years were 12.2 and 4.4 in add-on and 15.0 and 3.7 in switch patients. In patients with normal baseline values, alanine aminotransferase elevations >3×upper limit of normal were more frequent in add-on (14.3%) versus switch patients (5.4%).ConclusionsTreat-to-target strategies could be successfully implemented with TCZ to achieve sustained remission, after which TCZ was stopped. Biologic-free remission was maintained for about 3 months, but most patients eventually flared. TCZ restart led to rapid improvement.Trial registration numberNCT00810199.

Objective To examine the imaging-detected mechanism of reduction of structural joint damage progression by tocilizumab (TCZ) in patients with rheumatoid arthritis (RA) using MRI. Methods In a substudy of a randomised, double-blind, phase 3b study (ACT-RAY) of biologic-naïve patients with RA who were methotrexate (MTX)-inadequate responders, 63 patients were randomised to continue MTX or receive placebo (PBO), both in combination with TCZ 8 mg/kg every 4 weeks, with optional additional disease-modifying antirheumatic drugs at week 24 if Disease Activity Score of 28 joints < 3.2. The most symptomatic hand was imaged with 0.2 Tesla extremity MRI at weeks 0, 2, 12 and 52. MR images were scored using Outcome Measures in Rheumatology–Rheumatoid Arthritis Magnetic Resonance Imaging Score. Predictors of week 52 erosion progression were determined by logistic regression analysis. Results TCZ + PBO (n=32) demonstrated mean improvements in synovitis from baseline to weeks 2 (−0.92; p=0.0011), 12 (−1.86; p0.80). Baseline synovitis and worsening of osteitis predicted erosion progression. Conclusions Rapid suppression of synovitis and osteitis with reduction in structural joint damage progression occurred with TCZ, as monotherapy or in combination with MTX, through week 52.

Objective.To determine whether disease activity and disability independently correlate with serious infection event (SIE) risk in a large rheumatoid arthritis (RA) cohort.Methods.The associations between SIE and Clinical Disease Activity Index (CDAI) and Health Assessment Questionnaire-Disability Index (HAQ-DI) in the Rheumatoid Arthritis Disease-Modifying Antirheumatic Drug Intervention and Utilization Study (RADIUS 1) cohort were evaluated using the Andersen-Gill model (a proportional HR model allowing > 1 event per patient).Results.Of 4084 patients with 347 SIE, 271 patients experienced ≥ 1 SIE. A 5-unit CDAI increase and 0.4-unit HAQ-DI increase corresponded to an increase in SIE risk with and without covariate adjustments. A 5-unit CDAI increase corresponded with a 7.7% increased SIE risk (adjusted HR 1.077, 95% CI 1.044–1.112, p < 0.0001) and a 0.4-unit HAQ-DI increase with a 30.1% increased risk (adjusted HR 1.301, 95% CI 1.225–1.381, p < 0.0001). Categorical analysis showed that more severe RA activity (even after controlling for disability) and disability were associated with an increased SIE risk.Conclusion.Increased RA disease activity and disability were each associated with a significantly increased SIE risk in the RADIUS 1 cohort, which could not be completely accounted for by disability.

This text provides essential information needed to serve the large population of young athletic patients with cartilage defects who are not yet candidates for joint arthroplasty. Nearly 350 illustrations facilitate the understanding of examination and operative techniques, including arthroscopic debridement, electrothermal chondroplasty, marrow stimulation, osteochondral autograft transfer (OATS/Mosaicplasty), autologous chondrocyte implantation, and osteochondral allografting. The text also addresses joint specific injuries in the shoulder, elbow, and ankle that are often neglected in other literature. Key Features: Reviews normal cartilage anatomy and cartilage response to injury to illuminate appropriate treatment techniques and healing processes. Covers non-operative techniques including analgesics, oral anti-inflammatory medications, neutraceuticals, and hyaluronic acid injections/viscosupplementation, allowing the clinician to expand treatment options. Descriptions of adjunctive procedures, such as meniscal transplant and corrective osteotomy. Provides insights on future directions in the detection and treatment of cartilage injuries.

Background Radiographs (hands ± feet) measured with total Sharp scores (TSS) are considered the reference standard for quantifying structural damage in RA clinical trials. Magnetic resonance imaging (MRI) is increasingly utilized due to its greater sensitivity to detect erosive damage, but responsiveness and discrimination of MRI measures for joint damage and inflammation are not fully characterized. In a systematic literature review (SLR), we identified the OMERACT RA hand/wrist MRI Score (RAMRIS) as the only validated MRI tool. 1 Objectives To evaluate responsiveness and discrimination of RAMRIS synovitis, osteitis/bone marrow edema (BME), and erosions, we conducted a meta-analysis of published RCT data. Methods RCTs utilizing 1.5T MRI and measuring at least one RAMRIS feature were identified. Level of evidence (LoE) was assessed using modified Cochrane Handbook criteria. Change data for RAMRIS measures were converted to weighted mean changes ± SDs, and analyzed per treatment type and time point. ANOVA, weighted effect size, and estimated sample sizes were calculated. Relative weighted effect sizes (wES, using sample size as weighting factor) for biologic versus DMARD+placebo and for Biologic+DMARD versus DMARD+placebo at each time point for each RAMRIS measure were estimated using the difference between weighted mean of mean changes between groups, divided by the mean of weighted standard deviation across treatment groups. Results Ten RCTs provided resp/discrim data: nine with moderate (5/9) to good (4/9) LoE reported sufficient data to contribute to meta-analysis; one had inadequate LoE. Sample size ranged from 11 to 146 RA patients. Interventions studied were 7 biologics, 2 novel therapies +/- DMARDs in active RA patients. The table shows weighted effect size and sample size estimates for synovitis, osteitis and erosions across time. Compared to placebo, synovitis improved (p Conclusions RAMRIS measures with 1.5T MRI provide consistent responsiveness and discrimination for synovitis and osteitis/BME, but not for erosions. References Woodworth TG et al. Arthritis Rheum 2012.64:1050 Acknowledgements UCLA research librarians Rikke Ogawa and Lisa Federer, and Bristol Myers Squibb for an unconditional research grant. Disclosure of Interest T. Woodworth: None declared, O. Morgacheva: None declared, L. Duan: None declared, O. Pimienta: None declared, O. Troum Grant/research support: Bristol Myers Squibb, president International Society for Musculoskeletal Imaging in Rheumatology (ISEMIR), N. Barroso: None declared, V. Ranganath Grant/research support: Bristol Myers Squibb, D. Elashoff: None declared, D. Furst Grant/research support: Abbvie, Actelion Pharmaceuticals US, Amgen, Bristol Myers Squibb, Gilead, GlaxoSmithKline, Novartis, Pfizer, Roche/Genentech, UCBPharma, Janssen Pharmaceutical Products DOI 10.1136/annrheumdis-2014-eular.3971

Background Rheumatoid arthritis (RA) treatment has shifted from reducing symptoms to earlier inhibition of disease progression, thus preventing irreversible structural damage and disability. Detection of synovitis (SYN), osteitis (OST), and erosions (ERO), utilizing magnetic resonance imaging (MRI) may facilitate an earlier decision to progress from traditional disease modifying anti-rheumatic drugs (DMARDs) to the addition of biologic therapy. Arresting joint damage within 3 to 6 months of RA treatment determined by MRI, a more sensitive imaging technique compared to conventional radiography, should lead to low disease activity or remission, and subsequent better patient outcome with less disability. Abatacept (ABA) is a selective co-stimulation modulator that prevents T cell co-stimulation through CD28 pathway by binding avidly to CD80/86 and is clinically effective in reducing joint inflammation and structural damage. Objectives Assess the impact of inhibition and progression of structural joint damage by ABA in patients (pts) with RA using MRI and x-rays. Evaluate the relationship between RA MRI scoring system (RAMRIS) mean changes for SYN, OST, ERO and clinical outcomes. Methods 12 moderate to severe RA pts, methotrexate (MTX)-inadequate responders and biologic naive, were dosed to continue stable MTX combined with ABA 125 mg subcutaneous (sc) weekly. The dominant hand (metacarpophalangeal joints 1-5)/wrist were imaged with low field (0.2T), extremity MRI at baseline (BL), weeks (wks) 12, and 24 and x-rays at BL and wk 24. MR images were assessed according to the Outcome Measures in Rheumatology (OMERACT) RAMRIS and x-rays by Genant score. Change in scores from BL through wk 24 was compared to evaluate early effects of ABA on joint inflammation and damage. Results BL mean RAMRIS scores showed low (OST) to moderate (SYN, ERO) disease severity in contrast to high disease activity by DAS28 (ESR). Despite the small number of patients included, decreased SYN was observed at wk 12 with continued significant suppression by wk 24. No significant changes from BL to wk 24 were seen in mean OST scores. Although reductions in ERO were observed at wk 12, a small non- statistically significant mean change (worsening) from BL to wk 24 was observed. BL SYN correlated strongly and significantly with swollen joint count (SJC) and physician global assessment (PGA). BL OST correlated with PGA, and ERO correlated with SJC and PGA. Conclusions Low-field, extremity MRI of only 12 pts was able to demonstrate suppression of synovitis by ABA at wk 12 with further improvement through wk 24 and suppression of erosion progression through wk 24. Low BL levels of osteitis may explain the lack of significant change in mean RAMRIS osteitis. References American College of Rheumatology Rheumatoid Arthritis Clinical Trials Task Force Imaging Group and Outcome Measures in Rheumatology Magnetic Resonance Imaging Inflammatory Arthritis Working Group. Arthritis Rheum. 2013;65(10):2513-23 Disclosure of Interest O. Troum Grant/research support: Bristol-Myers Squibb, Consultant for: Bristol-Myers Squibb, O. Pimienta: None declared, L. Duan: None declared, J. Crues: None declared, C. Peterfy Consultant for: Bristol-Myers Squibb DOI 10.1136/annrheumdis-2014-eular.5001

Background 24-week data from ACT-RAY comparing an add-on strategy (TCZ+MTX) with a switch strategy (TCZ+placebo [PBO]) in MTX-IR patients have been previously reported, demonstrating relevant clinical and radiographic benefit without a statistically significant difference between the 2 groups. Longer-term data are needed to assess the 2 strategies over time and the effect of the protocol-specified treat-to-target strategy after Week 24. Objectives To assess the 52 week efficacy and safety of a TCZ-based adaptive treatment strategy with and without MTX in adult patients with moderate to severe RA and an inadequate response to MTX. Methods ACT-RAY is a phase 3b clinical trial. Patients on stable doses of MTX were randomized to either add TCZ 8 mg/kg IV every 4 weeks to their existing MTX or switch to TCZ 8 mg/kg IV every 4 weeks with oral PBO. Open-label DMARDs other than MTX were added at Week 24 or later, usually if DAS28 was >3.2, maintaining blinding of MTX/PBO. Groups are labeled “TCZ+MTX” and “TCZ+PBO” despite treatment modifications in both groups. Results 556 patients were randomized, with 85% completing 52 weeks of treatment. Baseline data were similar between the 2 groups except for Genant-modified Sharp Score, which was higher in the TCZ+PBO group. Between weeks 24 and 52, the proportion of patients receiving DMARD intensification was comparable in the TCZ+MTX and TCZ+PBO arms (29% vs 33%). Efficacy results are shown in the table. Efficacy was maintained or improved from Week 24 to 52. Most patients had no radiographic progression from baseline to 52 weeks >1.5 (smallest detectable change [SDC]). Rates of SAEs and serious infections per 100 PY were 14.2 and 4.9 for TCZ+MTX and 17.7 and 6.3 for TCZ+PBO, respectively. In patients with normal baseline values, ALT elevations >60U/L were observed in 36% of TCZ+MTX and 17% of TCZ+PBO patients. Antidrug antibodies (ADAs) were detected in 4.7% of patients (10/215) in the TCZ+MTX group and 5.4% (11/204) in the TCZ+PBO group up to week 52. Neutralizing ADAs were detected in 3.7% of patients (8/215) in the TCZ+MTX group and 4.4% (8/204) in the TCZ+PBO. Conclusions Clinical improvements at Week 24 in both groups were maintained or further improved up to Week 52, with the proportion of patients receiving DMARD intensification comparable between TCZ+MTX and TCZ+PBO. The vast majority of patients showed no radiographic progression of structural damage. The proportion of patients with ADAs was similar in both groups. Generally there were no differences in safety between the 2 groups. These data support the possibility of using TCZ monotherapy in patients with contraindications or intolerance to MTX. Disclosure of Interest M. Dougados Grant/Research support from: Roche, Consultant for: Roche, K. Kissel Employee of: F. Hoffmann-La Roche Ltd., P. Conaghan Grant/Research support from: Centocor Inc., Roche, Speakers Bureau: Astra Zeneca, Bioberica, Bristol-Meyers Squibb, Centocor Inc., Merck, Novartis, Pfizer, Roche, E. Martin-Mola Consultant for: Abbott Immunology, Roche MSD, Pfizer, UCB, G. Schett Consultant for: Roche, H. Amital: None Declared, R. Xavier Consultant for: Pfizer, Speakers Bureau: Pfizer, Roche, Merck, O. Troum Grant/Research support from: Genentech, Consultant for: Genentech, C. Bernasconi Employee of: F. Hoffmann-La Roche Ltd., T. J. Huizinga Consultant for: Abbott Immunology, Axis Shield Diagnostics, Biotest AG, Bristol-Meyers Squibb, Crescendo Bioscience, Roche, Novartis, Schering-Plough, UCB, Wyeth-Pfizer

Background While radiographic scoring of erosions and joint space narrowing (JSN) of the hand/wrist is standard to evaluate RA joint damage for regulatory approval of DMARDs, MRI is now also used to examine joint inflammation/damage in clinical trials. MRI field strength impacts feasibility, image quality and cost. Measurement methods initially used ≥1.0 tesla (T) MRI, requiring large machines and specialized space. Low field ( Objectives To report results of an SLR examining if Outcome Measures in Rheumatology Clinical Trials (OMERACT) RA MRI scoring (RAMRIS) is validated for low field (LF) images of RA wrist/hand. Methods We searched PubMed with Cochrane hedge for articles from 1970 to Aug 2012 using search terms with relevant data. These included: demographics/RA features in adults, MRI field strength ( Results 35 LF MRI articles met criteria for extraction. RAMRIS was most often used, as with our previous SLR evaluating ≥1.0T MRI. Altogether, 16 articles using Number of articles providing validity data for RAMRIS measurement with LF MRI Conclusions Using a rigorous PRISMA-compliant SLR to examine low field MRI/RAMRIS of the RA wrist/hand, we found 0.2T MRI is partially validated to measure synovitis, BME/osteitis and erosions. To finalize validation, evidence for discrimination between treatment groups for synovitis, BME, erosions, and discriminant construct validity for erosions are needed. Acknowledgements This work was supported by an unrestricted educational grant from Bristol Myers Squibb Disclosure of Interest O. Troum Grant/research support from: Abbott, Amgen, Bristol Myers Squibb, Centocor, Novartis, Pfizer, Roche/Genentech, Consultant for: Abbott, Amgen, Centocor, Pfizer, Roche/Genentech, Speakers bureau: Abbott, Amgen, Bristol Myers Squib, Pfizer, Roche/Genentech, UCB, O. Pimienta Grant/research support from: Bristol Myers Squibb, T. Woodworth Grant/research support from: Bristol Myers Squibb, O. Morgacheva Grant/research support from: Bristol Myers Squibb, V. Ranganath Grant/research support from: Bristol Myers Squibb, NIH, UCB, Consultant for: UCB, D. Furst Grant/research support from: Abbott, Actelion, Amgen, Bristol Myers Squibb, Gilead, GSK, NIH, Novarts, Pfizer, Roche/Genentech, UCB, Consultant for: Abbott, Actelion, Amgen, Bristol Myers Squibb, Bogenldec, Centocor, Gilead, GSK, NIH, Novartis, Pfizer, Roche/Genentech, UCB, Speakers bureau: Abbott, Actelion, UCB (CME only)