Showing papers by "Daniel Aletaha published in 2017"

EULAR definition of arthralgia suspicious for progression to rheumatoid arthritis

Abstract: BACKGROUND: During the transition to rheumatoid arthritis (RA) many patients pass through a phase characterised by the presence of symptoms without clinically apparent synovitis. These symptoms are ...

Evaluation of newly proposed remission cut-points for disease activity score in 28 joints (DAS28) in rheumatoid arthritis patients upon IL-6 pathway inhibition.

Abstract: Stringent remission criteria are crucial in rheumatoid arthritis (RA) assessment. Disease activity score in 28 joints (DAS28)-remission has not been included among American College of Rheumatology/European League Against Rheumatism definitions, because of its association with significant residual disease activity, partly due to high weighting of acute-phase reactants (APR). New, more stringent cut-points for DAS28-remission have recently been proposed that are suggested to reflect remission by clinical and simplified disease activity indices (clinical disease activity index (CDAI), simple disease activity index (SDAI)). However, their stringency in therapies directly influencing APR, like IL-6-blockers, has not been tested. We tested the new cut-points in patients with RA receiving tocilizumab. We used data from randomised controlled trials of tocilizumab and evaluated patients in remission according to new DAS28-C-reactive protein (DAS-CRP) and DAS-erythrocyte sedimentation rate (DAS-ESR) cut-points (1.9 and 2.2). We assessed their disease activity state using the CDAI, SDAI and Boolean criteria and analysed their individual residual core set variables, like swollen joint counts (SJC28). About 50% of patients in DAS28-CRP-remission (<1.9) fell into higher disease activity states when assessed with CDAI, SDAI or Boolean criteria. Also, 15% had three or more (up to eight) SJC. Even higher disease activity was seen in patients classified as being in DAS28-ESR-remission (<2.2). Even with new, more stringent cut-points, DAS28-remission is frequently associated with considerable residual clinical disease activity, indicating that this limitation of the DAS28 is related to score construction rather than the choice of cut-points.

Brief Report: Remission Rates With Tofacitinib Treatment in Rheumatoid Arthritis: A Comparison of Various Remission Criteria.

Abstract: Objective Tofacitinib is an oral JAK inhibitor that is used for the treatment of rheumatoid arthritis (RA) In previous clinical trials of tofacitinib, a Disease Activity Score in 28 joints (DAS28)–based analysis was used to assess outcomes In this study, remission rates according to various remission criteria were evaluated across 5 phase III randomized controlled studies Methods In all 5 studies, tofacitinib was administered at a dosage of 5 mg twice daily or 10 mg twice daily, either as monotherapy or with background methotrexate or other conventional synthetic disease-modifying antirheumatic drugs One of the studies included adalimumab 40 mg once every 2 weeks In addition to the 4-variable DAS28 using the erythrocyte sedimentation rate (DAS28-4[ESR]), a primary efficacy variable used in the phase III studies, disease activity was assessed post hoc by the 4-variable DAS28 using the C-reactive protein level (DAS28-4[CRP]), the Clinical Disease Activity Index (CDAI), the Simplified Disease Activity Index (SDAI), and Boolean-based assessment Results A total of 3,306 patients were analyzed (1,213 of these patients received tofacitinib 5 mg twice daily, 1,212 received tofacitinib 10 mg twice daily, 679 received placebo, and 202 received adalimumab 40 mg every 2 weeks) Remission rates varied according to the criteria used, with higher rates in the active-treatment groups for the DAS28-4(CRP) than for other scores At month 3, remission rates with tofacitinib 5 mg twice daily were 18–22% using the DAS28-4(CRP), 5–10% using the DAS28-4(ESR), 4–7% using the SDAI, 5–6% using the CDAI, and 2–7% using the Boolean-based method In contrast, the remission rates with placebo varied from 0% to 7%, with small differences between the DAS28-4(ESR) and the DAS28-4(CRP) Conclusion Although tofacitinib at dosages of 5 mg twice daily and 10 mg twice daily was effective compared with placebo in achieving disease remission, regardless of the disease activity measure, remission rates were substantially higher when the DAS28-4(CRP) was used The presence or absence and type of acute-phase reactants in remission criteria were significant contributors to remission rates across treatment groups This finding has important consequences for trial design and clinical practice

The effects of structural damage on functional disability in psoriatic arthritis

Abstract: Background Functional outcomes are central in patients with chronic inflammatory musculoskeletal diseases. In a secondary data analysis of the GO-REVEAL trial (NCT00265096), we investigated wether structural damage is linked to functional impairment in patients with psoriatic arthritis (PsA), a link that is still elusive in this disease. Methods We analysed 363 patients enrolled in the GO-REVEAL study and obtained modified Sharp/van der Heijde Scores (mSvdHS) from X-rays performed at baseline, after 24, 52 and 104 weeks. Using longitudinal analyses, we assessed the effect of total mSvdHS (and its subscores, joint space narrowing (JSN) and erosions (ERO)) on functional status (measured by the Health Assessment Questionnaire) in all patients and in those attaining remission (n=117). Furthermore, we analysed wether structural damage reduces the responsiveness of functional limitations to treatment in a subgroup of responders who had functional impairment at baseline (n=67). Additionally, internal and external validation analyses were performed. Results The effect of damage on function was seen in the disease activity-adjusted models using total mSvdHS (p=0.005), JSN (p=0.019) and ERO (p=0.001) as well as in the remission analyses for mSvdHS (p=0.029) and JSN (p=0.010), respectively. Functional responsiveness was limited by increasing total mSvdHS (p=0.010), JSN (p=0.002) and ERO (p=0.040). The results were validated using other functional outcomes and in an independent clinical cohort. Conclusions In PsA, structural damage, particularly JSN, has implications for physical function. Functional outcomes have an irreversible component that is strongly related to the extent of joint destruction. This needs to be considered when targeting functional outcomes in clinical practice.

Different Rating of Global Rheumatoid Arthritis Disease Activity in Rheumatoid Arthritis Patients With Multiple Morbidities.

Abstract: Objective To quantify differences and determine the factors contributing to the difference in patient global assessment of rheumatoid arthritis (RA) disease activity (PtGA) between RA patients with multiple morbidities (RA-MM) and those with RA only. Methods We compared the PtGA between RA-MM patients and those with RA only, followed up in a longitudinal cohort (n = 1,040). In analyses performed on RA-MM patients (n = 575) and those with RA only (matched for swollen joint count, tender joint count, evaluator global assessment, and disease duration), the mean difference in PtGA (ΔPtGA) between the 2 groups was assessed. The contribution of patient characteristics to the explained variation of ΔPtGA in the matched cohort was calculated as semipartial R2 and summarized as the percentage of the total R2 in linear regression models. Results RA-MM patients reported higher (or worse) PtGA, with an increased PtGA associated with more morbidities (P for linear trend < 0.01); this relationship remained significant after adjustment for disease activity, age, and disease duration. After matching 294 RA-MM patients to those with RA only, the pairwise comparison of mean PtGA (on a scale of 0–100 mm) was significantly higher (worse) for RA-MM patients (mean ± SD 30.5 ± 24.3) versus those with RA only (25.6 ± 22.9) (mean ΔPtGA 4.9 ± 26.7; P < 0.01 by paired t-test). Variables uniquely contributing to ΔPtGA were fatigue (18%), pain (17%), and modified Health Assessment Questionnaire scores (9%). Conclusion In RA patients with multiple morbidities, the perception of RA disease activity as measured by the PtGA might be impacted by the burden of multiple diseases in one individual. RA-MM patients have higher (worse) levels of PtGA scores compared to patients with RA only. The difference in PtGA is mainly explained by differences in fatigue and pain.

Comparative Assessment of the Different American College of Rheumatology/European League Against Rheumatism Remission Definitions for Rheumatoid Arthritis for Their Use as Clinical Trial End Points

Abstract: Objective The American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) have defined remission using Boolean- or index-based criteria (i.e., a Simplified Disease Activity Index [SDAI] score of ≤3.3). We undertook this study to compare definitions of remission to inform choice of end points for future rheumatoid arthritis (RA) clinical trials, and we also included in our comparison the remission criterion of a score of ≤2.8 on the Clinical Disease Activity Index (CDAI). Methods We performed post hoc analyses on clinical remission rates using data from 2 infliximab trials (the ASPIRE [Active-Controlled Study of Patients Receiving Infliximab for the Treatment of Rheumatoid Arthritis of Early Onset] and ATTRACT [Anti–Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy] trials) and 1 golimumab trial (the GO-FORWARD trial). We investigated stringency of the different remission definitions, their power to discriminate between active drug and comparator, and aspects of their internal and external validity. We also investigated population determinants of discriminatory power for a particular remission end point. Results In patients with early RA (the ASPIRE trial), ACR/EULAR Boolean, CDAI, and SDAI remission rates at 6–7 months were 4–6% for methotrexate (MTX) alone versus 11–14% for infliximab plus MTX. In patients with MTX-refractory active RA (the ATTRACT and GO-FORWARD trials), remission rates were ≤1% for comparator (add-on of placebo) versus 4–6% for add-on of infliximab in the ATTRACT trial and ≤3% for comparator (add-on of placebo) versus 11–13% for add-on of golimumab in the GO-FORWARD trial. Existing remission cut points of different measures were generally comparable, with the Boolean criteria being somewhat more stringent than the SDAI and CDAI criteria. Remission rates were similar across definitions, as was average statistical power (CDAI, 55.6%; Boolean, 59.9%; SDAI, 62.6%). Conclusion Remission is an ambitious primary end point for RA clinical trials, to be reserved for selected scenarios based on power considerations. The ACR/EULAR definitions are interchangeable, with slightly higher stringency of Boolean criteria over index-based criteria.

Abstracts from The College of Podiatry Annual Conference 2016

Abstract: s from The College of Podiatry Annual Conference 2016 Glasgow, Scotland. 17-19 November 2016 Published: 7 March 2017 1 Educational tool and point-of-care tests to assist antibiotic prescribing decisions for diabetic foot ulcer infections (INDUCE study) John Ingram, Scott Cawley, Angela Jones, Elinor Coulman, Clive Gregory, Tim Pickles Department of Dermatology and Academic Wound Healing, Division of Infection & Immunity, Cardiff University, Cardiff, UK; Podiatry Department, Cardiff and Vale University Health Board, Cardiff, UK; Centre for Trials Research, Cardiff University, Cardiff, UK; Division of Population Medicine, School of Medicine, Cardiff University, Cardiff, UK Correspondence: Angela Jones Journal of Foot and Ankle Research 2017, 10(Suppl 1):1 Background Assessing diabetic foot ulcers (DFUs) for infection is difficult because clinical symptoms and signs may be masked by neuropathy and vasculopathy and there are no objective tests available at point of care to guide clinicians. Empirical prescription of antibiotics compromises antibiotic stewardship, while missing early infection may lead to severe infection and amputation. In 2011-12, the cost of managing DFUs and associated amputations borne by NHS England was £650 million, nearly 1% of its budget. Our INDUCE study had two aims: (1) to develop an online educational tool for DFU infection and (2) to conduct a pilot study investigating C-reactive protein (CRP) and procalcitonin from venous blood and calprotectin from wound exudate as inflammatory biomarkers of mild DFU infection. Methods Yola software was used to develop an online educational tool covering DFU history and examination, arterial assessment, microbiology, radiology and management of osteomyelitis. The tool contains links to NICE guidance and other relevant learning resources. A quiz using patient scenarios is included. Feedback from podiatrists was elicited by questionnaires and a focus group. Patients with non-infected or mildly infected DFUs were recruited from community podiatry clinics in 2 UK regions. Exclusion criteria included immunosuppression or receipt of antibiotics within the previous 2 weeks. Antibiotics were prescribed based on clinical judgement at the baseline assessment. Our gold standard defining DFU infection was the clinician’s judgement one week later, while still blinded to test results, factoring in the response to antibiotic therapy, if prescribed. All 3 inflammatory biomarkers were measured at weeks 0 and 1, including assessment of CRP using a point-of-care device. Results Feedback regarding the educational tool from end-users ranging from trainee to senior podiatrists was very positive. The main improvement requested was a printable certificate after successful completion of the quiz and provision of CPD points. Between September 2014 and September 2015, the INDUCE study recruited 67 patients with DFUs, from a total of 363 potential participants. © The Author(s). 2017 Open Access This artic International License (http://creativecommons reproduction in any medium, provided you g the Creative Commons license, and indicate if (http://creativecommons.org/publicdomain/ze Primary endpoints were available for 37 participants with non-infected ulcers and 28 with mild infection, following early study withdrawal by one patient in each group. Median CRP was slightly higher in the infected ulcer group, 7.50 mg/ml compared to 6.00 mg/ml for noninfected ulcers, but the area under the receiver operating characteristic curve (AUROC) was only 0.52, demonstrating poor predictive efficacy. Most of the procalcitonin results were below the lower limit of the assay and levels were lower in the infected DFU group. Median calprotectin levels were nearly doubled in infected ulcers, 1437 ng/ml compared with 879 ng/ml in non-infected DFUs, but with an insufficient AUROC of 0.56. Conclusions Feedback from a range of podiatrists confirmed that assessment of DFU infection remains challenging and showed that the INDUCE tool is a useful learning resource. The tool will be made freely available via the internet. Based on their sensitivity and specificity, neither venous CRP or procalcitonin should be pursued as biomarkers of DFU infection, alone or in combination. Calprotectin in wound exudate may have value, but only in combination with other biomarkers. 2 Shoe hardness and gait Him Shun Hinson Kei, Paul Fletcher, Mike Curran Faculty of Health and Society, University of Northampton, Northampton, UK Correspondence: Him Shun Hinson Kei Journal of Foot and Ankle Research 2017, 10(Suppl 1):2 Introduction This study will have implications for any healthcare professionals who aim to alter patient’s gait with footwear. This study examines the reliability of Dartfish 8 with Canon 700D in the measurement of joint motion and percentages of different stance phases. It also serves as a pilot study to investigate the influence of sole hardness on the walking gait to recommend footwear and prevent injury. Methods 14 participants walked along a walkway at their preferred speed under four conditions of different sole hardness (barefoot, 58 shore C, 68 shore C and 74 shore C). The sequence of the shoe conditions was randomly assigned. Ankle joint and first metatarsophalangeal joint (1st MTPJ) maximum dorsiflexion and the percentage of different stance phases were determined with Dartfish 8.0. Intra-class Correlation Coefficient Test was carried out to check if the two measures for each angle concerned and each percentage concerned had absolute agreement using the two-way mixed model. Statistical techniques were used to identify differences among different sole conditions. Results The presented protocol was reliable in the measurement of ankle and 1st MTPJ maximum dorsiflexion but not as accurate in the measurement of the percentages of different stance phases. Left ankle le is distributed under the terms of the Creative Commons Attribution 4.0 .org/licenses/by/4.0/), which permits unrestricted use, distribution, and ive appropriate credit to the original author(s) and the source, provide a link to changes were made. The Creative Commons Public Domain Dedication waiver ro/1.0/) applies to the data made available in this article, unless otherwise stated. Journal of Foot and Ankle Research 2017, 10(Suppl 1):10 Page 2 of 11 maximum dorsiflexion was greater with moderate soles compared to hard soles and with soft soles compared to barefoot. The Differences observed in 1st MTPJ maximum dorsiflexion were minimal. The percentage of midstance for the left foot was larger in the barefoot condition than the soft and moderate sole conditions. Conclusion: For the 14 participants in this pilot study, moderate soles encourage left ankle range of motion (ROM) whereas hard soles restrict left ankle ROM. A limited range of motion has been cited as a cause of injury and a risk factor for diabetic ulceration. This pilot study may be particularly important in the management of diabetic patients and patients who walk for a long time routinely. The effect of sole hardness on joint motion and gait phases still warrant further investigation. It may be worth examining the long-term effect of sole hardness on different joints and the walking gait. It is hoped that optimal sole hardness could be recommended to patients based on their age, weight and biomechanical presentation in the future. 3 Plantar loading patterns of elite rowers on a fixed ergometer: Comparison of a commercially available rowing specific shoe to a training shoe

Clinical and economic analysis of outcomes of dose tapering or withdrawal of tumor necrosis factor-α inhibitors upon achieving stable disease activity in rheumatoid arthritis patients.

Abstract: OBJECTIVE To compare the real-world, 5-year clinical and cost impact of maintaining treatment with the tumor necrosis factor-α inhibitors (anti-TNFs) adalimumab, etanercept, or infliximab vs dose tapering or withdrawal in rheumatoid arthritis (RA) patients who have achieved remission (defined as a 28-joint count Disease Activity Score [DAS28] < 2.6) or low disease activity (LDA; DAS28 < 3.2). METHODS Using a 5-year Markov model with 1-month cycle length, we examined the clinical and cost impact of three treatment strategies: withdrawal, tapering, or maintenance of anti-TNFs among RA patients in remission or who have achieved LDA. This model assessed the time to loss of disease control, time to regaining control after treatment reinitiation, and associated medical and anti-TNF costs. To determine the risk of losing disease control, 14 studies (2309 patients) were meta-analyzed, adjusted for treatment strategy, anti-TNF, RA patient type (early or established RA), and model entry criterion (remission or LDA). RESULTS Anti-TNF withdrawal and tapering incurred comparable 5-year total costs (€37,900-€59,700 vs €47,500-€59,200), which were lower than those incurred by anti-TNF maintenance (€67,100-€72,100). Established RA patients had higher total costs than early RA patients (€45,900-€72,100 vs €37,900-€71,700). Maintenance was associated with the longest time to loss of disease control (range, 27.3-47.1 months), while withdrawal had the shortest (range, 6.9-30.5 months). CONCLUSION Dose tapering or withdrawal of anti-TNFs results in similar reduction of health care costs but less time in sustained disease control compared to maintaining therapy. Future research is needed to understand the long-term clinical consequences of these strategies and patient preferences for treatment withdrawal.

FRI0498 Outcomes associated with achievement of various treatment targets in patients with psoriatic arthritis receiving adalimumab

Abstract: Background Various instruments are currently used for disease activity and outcome assessment in psoriatic arthritis (PsA). Some measures attempt to incorporate the total spectrum of psoriatic disease manifestations [eg, minimal disease activity (MDA)] while others focus on arthritis assessments [eg, disease activity index for PsA (DAPSA)]. Whether in patients (pts) with PsA it is sufficient to primarily consider joint disease aspects remains unclear. Objectives To compare DAPSA remission and low disease activity (LDA) with MDA and very low disease activity (VLDA) for the presence of residual abnormalities of the respective composing variables. Methods This post hoc analysis included pts with PsA receiving adalimumab (ADA) in one of two multicenter studies: ADEPT was a 24-week (wk), randomized, double-blind, placebo-controlled trial; ACCLAIM was a 12-wk, open-label study conducted in Canada in care settings that reflected usual practice. Frequencies of DAPSA remission/LDA and MDA/VLDA were summarized, and the individual PsA manifestations within these states were assessed. DAPSA was summed from the following continuous variables: swollen (66) and tender (68) joints, pt global assessment (PtGA, cm), pt pain (PP, cm), and C-reactive protein (CRP, mg/dL). DAPSA remission was defined as ≤4 and DAPSA LDA as >4 and ≤14. MDA criteria were as follows: ≤1 tender, ≤1 swollen joint, ≤1 entheseal point, PP ≤15mm, PtGA ≤20mm, HAQ ≤0.5, and PASI ≤3. MDA was calculated as fulfilling 5 of the 7 criteria, and VLDA calculated as fulfilling all 7 criteria. Data were as observed. Results Among 151 pts receiving ADA in ADEPT, 33 (22%) each achieved DAPSA remission and LDA at wk 24, and 20 (14%) and 11 (7%) achieved MDA and VLDA, respectively. Pts achieving DAPSA LDA appeared to mirror those in MDA, with the exception of experiencing numerically higher PP, PtGA, and PASI scores at wk 24 (Table). Pts in DAPSA LDA did experience numerically lower SJC when compared with the MDA achievers, and, like MDA achievers, displayed little residual enthesitis. Only VLDA, but not MDA, could match the stringency of DAPSA remission, a finding that was confirmed through analysis of the ACCLAIM cohort. However, VLDA allowed for numerically higher residual PP and PtGA levels when compared with DAPSA remission. Importantly, residual enthesitis did not differ among pts achieving DAPSA remission or VLDA. Irrespective of disease activity assessment, pts receiving ADA displayed little to no radiographic progression. Conclusions In the ADEPT and ACCLAIM cohorts, pts who achieved DAPSA remission or VLDA demonstrated similar outcomes with respect to the individual components of both scores, despite the omission of several of these within the DAPSA. Given the DAPSA9s continuous nature, its use may offer a good alternative to fulfillment of the VLDA criteria, but these results require confirmation in different pt populations. Acknowledgements AbbVie: study sponsor, contributed to design, data collection, analysis, interpretation, and abstract writing, review, and approval. Medical writing: Ben Wolfe of AbbVie. Disclosure of Interest J. Smolen Grant/research support from: AbbVie, Inc., Consultant for: AbbVie, Inc., D. Aletaha Grant/research support from: AbbVie, Inc., Pfizer, Grunenthal, Merck, Medac, UCB, Mitsubishi/Tanabe, Janssen, and Roche, Consultant for: AbbVie, Inc., Pfizer, Grunenthal, Merck, Medac, UCB, Mitsubishi/Tanabe, Janssen, and Roche, D. Gladman Grant/research support from: AbbVie, Inc., Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Pfizer, Novartis, and UCB, Y. Zhang Shareholder of: AbbVie, Inc., Employee of: AbbVie, Inc., F. Ganz Shareholder of: AbbVie, Inc., Employee of: AbbVie, Inc.

SAT0194 Sirukumab integrated safety in rheumatoid arthritis patients: analysis of the sirround phase 3 data

Abstract: Background Sirukumab (SIR), a human monoclonal antibody that selectively binds the IL-6 cytokine, is in development for the treatment of rheumatoid arthritis (RA). Efficacy of SIR was shown in several phase 3 trials in RA patients (pts; SIRROUND program). Objectives To analyze safety data from completed/ongoing studies in the SIRROUND program. Methods Safety comparisons included SIR 50mg q4w and 100mg q2w doses vs placebo (pbo) in the pbo-controlled period (Wk 0–18) of 2 phase 3 studies. A long-term comparison of the safety of SIR 50mg q4w and 100mg q2w for the entire program was also performed. Results In phase 3 studies, 2926 pts received SIR for up to 3.4y (median duration, 1.46y). During Wk 0–18, there were more adverse events (AEs), AEs leading to discontinuation, and serious AEs (SAEs) with SIR vs pbo, with cumulative rates of SAEs remaining constant over time (Table). In general, no dose effect with SIR was observed in the 18-wk or long-term analysis. Mortality rates were similar across treatment groups through 18 wks and remained stable in long-term analysis. Serious infections were more frequent in SIR-treated pts vs pbo during Wk 0–18, with similar rates through long-term analysis. Rates of gastrointestinal (GI) perforations and malignancies were low and similar across groups during the 18-wk and long-term analysis; major adverse cardiovascular event (MACE) rates were similar through 18 wks and numerically higher with SIR 50mg q4w vs 100mg q2w in long-term analysis. Conclusions SIR is well tolerated in pts with moderately to severely active RA. Overall, no dose relationship was observed between SIR 50mg q4w and 100mg q2w for types or frequencies of AEs. Disclosure of Interest D. Aletaha Grant/research support from: AbbVie, Pfizer, Grunenthal, Merck Medac, UCB, Mitsubishi/Tanabe, Janssen, and Roche, Consultant for: AbbVie, Pfizer, Grunenthal, Merck Medac, UCB, Mitsubishi/Tanabe, Janssen, and Roche, C. Thorne Grant/research support from: AbbVie, Amgen, Celgene, Lilly, Novartis, Pfizer, Sanofi, and UCB, Consultant for: AbbVie, Amgen, Celgene, Centocor, Genzyme, Hospira, Janssen, Lilly, Medexus/Medac, Merck, Novartis, Pfizer, Sanofi, and UCB, Speakers bureau: Medexus/Medac, M. Schiff Consultant for: AbbVie, Bristol-Myers Squibb, Eli Lilly, Johnson & Johnson, UCB, Speakers bureau: AbbVie, M. Harigai Grant/research support from: AbbVie Japan, Astellas Pharma, Bristol-Myers Squibb, Chugai Pharmaceutical, Eisai, Mitsubishi Tanabe Pharma, Ono Pharmaceuticals, Santen Pharmaceutical, Takeda Pharmaceutical, UCB Japan, Teijin Pharma, Consultant for: AbbVie Japan, Janssen Pharma, Chugai Pharmaceutical, Teijin Pharma, Eli Lilly Japan, and Zenyaku Kogyo, R. Rao Shareholder of: GlaxoSmithKline, Employee of: GlaxoSmithKline, N. Goldstein Employee of: Janssen Research & Development, LLC, B. Cheng Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC, C. Cohen Employee of: GlaxoSmithKline, B. Hsu Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC, K. Brown Shareholder of: GlaxoSmithKline, Employee of: GlaxoSmithKline

OP0108 Inhibition of radiographic progression in psoriatic arthritis by adalimumab independent of the control of clinical disease activity

Abstract: Background Patients (pts) with psoriatic arthritis (PsA) may experience structural damage and irreversible functional impairment if not treated appropriately. Treatment with TNF inhibitors in rheumatoid arthritis (RA) pts showed inhibition of radiographic progression larger than expected based on the control of clinical disease activity.1 Preliminary results showed that such a disconnect phenomenon may also be observed in PsA pts following treatment with adalimumab (ADA).2 Objectives The objective of this analysis was to further examine the relationship between inhibition of radiographic progression and control of clinical disease activity using different disease activity measures following treatment with originator ADA versus placebo (PBO) in pts with active PsA. Methods ADEPT3 was a 24-week (wk), randomized, double-blind trial comparing the safety and efficacy of ADA with PBO in pts with active PsA. In this post hoc analysis, radiographic progression, defined as change from baseline (BL) to wk 24 in modified total Sharp score (ΔmTSS) >0.5, was calculated in pts with evaluable radiographs at both time points. Pts were classified based on achieving minimal disease activity (MDA) and different subcategories of disease activity (remission, low, moderate, or high) based on time-averaged (TA) DAS28(CRP), DAPSA, and PASDAS. The associations between ΔmTSS and disease activity were assessed by Pearson (rp) or Phi (rφ) correlation coefficients. Results Of the 296 pts (ADA, N=144; PBO, N=152) included in this analysis, higher proportions of pts receiving ADA compared with PBO achieved MDA and remission/low disease activity status across all the outcome measures. There was a significant interaction between treatment and disease activity status with respect to radiographic progression (P Conclusions The results showed that the relationship between disease activity as determined by various outcome measures differed between ADA and PBO treated pts. ADA provided inhibition of radiographic progression which was somewhat larger and independent of the control of clinical disease activity. This supports the disconnect phenomenon in PsA following ADA treatment. References Landewe R, et al. Arthritis Rheum. 2006; 54:3119–25. Mease PJ, et al. Arthritis Rheum. 2010; 62 (suppl 10). Mease PJ, et al. Arthritis Rheum. 2005; 52:3279–89. Acknowledgements AbbVie funded the study (NCT00646386), contributed to its design, and participated in data collection, analysis and interpretation of the data, and in writing, review, and approval of the publication. Medical writing support was provided by Deepa Venkitaramani, PhD, of AbbVie. Disclosure of Interest R. Landewe Grant/research support from: Abbott, Amgen, Centocor, Novartis, Pfizer, Roche, Schering-Plough, UCB and Wyeth, Consultant for: Abbott/AbbVie, Ablynx, Amgen, Astra-Zeneca, BMS, Janssen (formerly Centocor), GSK, Merck, Novo-Nordisk, Novartis, Pfizer, Roche, Schering-Plough, TiGenics, UCB, and Wyeth; is Director of Rheumatology Consultancy BV, Speakers bureau: Abbott, Amgen, Centocor, Novartis, Pfizer, Roche, Schering-Plough, UCB and Wyeth, C. Ritchlin Grant/research support from: Amgen, Janssen, Pfizer, and UCB, Consultant for: AbbVie, Amgen, Janssen, Lilly, Pfizer, and UCB, L. Coates Grant/research support from: AbbVie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer, Sun Pharma, and UCB, Consultant for: AbbVie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer, Sun Pharma, and UCB, Speakers bureau: AbbVie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer, Sun Pharma, and UCB, D. Aletaha Grant/research support from: AbbVie, BMS, Janssen, Lilly, Merck, Medac, Mitsubishi/Tanabe, Pfizer, Roche, and UCB, Consultant for: AbbVie, BMS, Janssen, Lilly, Merck, Medac, Mitsubishi/Tanabe, Pfizer, Roche, and UCB, Speakers bureau: AbbVie, BMS, Janssen, Lilly, Merck, Medac, Mitsubishi/Tanabe, Pfizer, Roche, and UCB, B. Guerette Shareholder of: AbbVie, Employee of: AbbVie, Y. Zhang Shareholder of: AbbVie, Employee of: AbbVie, F. Ganz Shareholder of: AbbVie, Employee of: AbbVie, M. Hojnik Shareholder of: AbbVie, Employee of: AbbVie

AB1245-HPR New health technologies and lifestyle management for patients with osteoarthritis

Abstract: Background Osteoarthritis (OA) is one of the most common chronic diseases of the elderly worldwide. It represents significant impairments in terms of quality of life [1]. It notably affects self-care-tasks, body-image, self-esteem, well-being, social-activities and relationships. A wide-ranged field of therapy concepts exist. Medication is often one part, but it cannot solve other existing problems due to OA [2]. The demographic trends combined with the growth of mobile devices among the older population suggest that using digital devices, as a platform for interventions in health, may be a viable way forward and open new opportunities in healthcare [2]. Objectives To (A) analyse the literature to assistive devices and applications for OA patients and (B) to evaluate existing health applications. Methods We performed a systematic literature review on this topic and explored existing mobile and web-based apps. The app findings were classified into those categories of the Activities of Daily Living Model, which were related to the impairments of OA. Results We identified 6 studies, which contained relevant information. The main results showed, that there is interest and willingness to utilize mobile Health solutions [3]; a positive impact of web-based interventions; the benefit of online social support regarding the level of patient empowerment [4], self-management, lifestyle, physical activity [5] and self-efficacy [6]. The app exploration results in 16 web-based, 15 iOS and 9 Android applications. The areas most commonly found were disease- and treatment information (n=23), forum, report, self-help groups (n=16), self- and disease-management (n=11), as well as nutrition tips (n=8). Conclusions The recent years have seen a dramatic growth of digital applications. Also, the scientific interest has grown and numerous studies emphasise the power of these solutions to support OA patient in all areas of lifestyle management. Further research is necessary, to investigate the benefit of web-based or mobile applications for persons with OA. References T. Aigner, S. Soder, Typisierung, Graduierung und Stadieneinteilung der Osteoarthrose: Histopathologische Begutachtung der Gelenkdegeneration, Z. Fur Rheumatol., 2008;67(1):32–40. J. Joe, G. Demiris, Older adults and mobile phones for health: A review, J. Biomed. Inform. 2013;46(5):947–954. S.J. Parker, S. Jessel, J.E. Richardson, M.C. Reid, Older adults are mobile too!Identifying the barriers and facilitators to older adults9 use of mHealth for pain management, BMC Geriatr. 2013;13(1):43. A. Allam, Z. Kostova, K. Nakamoto, P. J. Schulz, The Effect of Social Support Features and Gamification on a Web-Based Intervention for Rheumatoid Arthritis Patients: Randomized Controlled Trial, J. Med. Internet Res. 2015;17(1):e14. H. Umapathy, K. Bennell, C. Dickson, F. Dobson, M. Fransen, G. Jones, D.J. Hunter, The Web-Based Osteoarthritis Management Resource My Joint Pain Improves Quality of Care: A Quasi-Experimental Study, J. Med. Internet Res. 2015;17(7):e167. K.R. Lorig, P.L. Ritter, D.D. Laurent, K. Plant, The internet-based arthritis self-management program: A one-year randomized trial for patients with arthritis or fibromyalgia, Arthritis Rheum. 2008;59(7):1009–1017. Disclosure of Interest None declared

Induction Of Sustained Remission In Early Inflammatory Arthritis With The Combination Of Infliximab Plus Methotrexate, Methotrexate Alone Or Placebo: The Dinora Trial

Abstract: Background Rheumatoid arthritis is a chronic form of inflammatory arthritis that is thought to have an early stage or reversibility with effective therapy (“window of opportunity”). Objectives In the present study, we explored the effects of induction therapy with anti-TNFα antibody infliximab (IFX) plus methotrexate (MTX) compared with MTX alone and with placebo (PL) in patients with very early inflammatory arthritis. Methods In an investigator-initiated, double-blind, randomized, placebo-controlled, multi-center trial, patients with synovitis of 12–16 weeks duration in at least 2 joints underwent one year of treatment with IFX in combination with MTX, MTX monotherapy or PL randomized in a 2:2:1 ratio. The primary endpoint was clinical remission after 1 year (sustained for at least two consecutive visits 8 weeks apart including week 54) with remission defined as no swollen joints, 0 - 2 tender joints and a C-reactive protein (CRP) level within the normal range ( Results See Table 1. 90 patients participated in the present study. At week 54 (primary endpoint), 32% of the patients in the IFX+MTX group achieved sustained remission compared with 14% on MTX alone and 0% on PL (Table). This difference was statistically significant for all three groups (p Conclusions These results indicate that patients with early arthritis can benefit from induction therapy with anti-TNF plus MTX compared to MTX alone, suggesting the existence of a window of opportunity where intensive treatment can alter the disease evolution Disclosure of Interest T. Stamm Grant/research support from: For all authors: DINORA was partly funded by a grant from Janssen (previously Centocor). TS: AbbVie, Consultant for: AbbVie, Novartis, Speakers bureau: AbbVie, Janssen, MSD, Novartis and Roche, K. Machold: None declared, D. Aletaha Grant/research support from: AbbVie, Pfizer, Grunenthal, Merck Medac, UCB, Mitsubishi/Tanabe, Janssen and Roche, Consultant for: AbbVie, Pfizer, Grunenthal, Merck Medac, UCB, Mitsubishi/Tanabe, Janssen and Roche, F. Alasti: None declared, P. Lipsky Consultant for: Janssen, EMD Serono, Astra Zeneca, UCB, Roche, Celgene, Sanofi and Horizon, but none of them relates to the content of this manuscript, D. Pisetsky: None declared, R. Landewe Grant/research support from: Abbott, Amgen, Centocor, Novartis, Pfizer, Roche, Schering-Plough, UCB and Wyeth, Consultant for: Abbott/AbbVie, Ablynx, Amgen, Astra-Zeneca, Bristol Myers Squibb, Celgene, Janssen (formerly Centocor), Galapagos, Glaxo-Smith-Kline, Novartis, Novo-Nordisk, Merck, Pfizer, Roche, Schering-Plough, TiGenix, UCB and Wyeth, Employee of: RL is director of Rheumatology Consultancy BV which is a registered company under Dutch law., Speakers bureau: Abbott/AbbVie, Amgen, Bristol Myers Squibb, Janssen (formerly Centocor), Merck, Pfizer, Roche, Schering-Plough, UCB and Wyeth, D. van der Heijde Consultant for: AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boeringer Ingelheim, Celgene, Daiichi, Eli-Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi and UCB, Employee of: DH is director of Imaging Rheumatology bv., A. Sepriano: None declared, M. Aringer Grant/research support from: MA9s institution is clinical trial site for AbbVie, Astra Zeneca, Boehringer Ingelheim, Novartis, Pfizer and Roche., Consultant for: AbbVie, Astra Zeneca, BMS, Chugai, GSK, Hexal, Lilly, MSD, Novartis, Pfizer, Roche, Sanofi and UCB, Speakers bureau: AbbVie, Astra Zeneca, BMS, Chugai, GSK, Hexal, Lilly, MSD, Novartis, Pfizer, Roche, Sanofi and UCB, D. Boumpas: None declared, G. Burmester Grant/research support from: AbbVie, BMS, UCB and Roche, Speakers bureau: MSD, UCB and Roche, M. Cutolo Grant/research support from: BMS, Horizon, Actelion, Celgene and MSD, Speakers bureau: Biogen, Mundipharm, Pfizer and Menarini, W. Ebener Consultant for: Novartis and Abbvie, W. Graninger: None declared, T. Huizinga Consultant for: Merck, UCB, Bristol Myers Squibb, Biotest AG, Pfizer, GSK, Novartis, Roche, Sanofi-Aventis, Abbott, Crescendo Bioscience, Nycomed, Boeringher, Takeda, Epirus and Eli Lilly, G. Schett Speakers bureau: BMS, Celgene, Chugai, Lilly, Roche and UCB, H. Schulze-Koops Speakers bureau: AbbVie, Actelion, AstraZeneca, Biogen International, Boehringer Ingelheim, BMS, Celgene, Celltrion, Chugai, Cinfa Biotech, GSK, Hospira, Janssen-Cilag, Lilly, MSD, Medac, Merck, Mundipharma, Novartis, Pfizer, Hexal Sandoz, Roche and UCB, P. P. Tak Employee of: PPT has become an employee of GlaxoSmithKline. GSK has not been involved in this study., F. Breedveld: None declared, J. Smolen Grant/research support from: Abbvie, Lilly, MSD, Pfizer and Roche, Consultant for: Abbvie, Amgen, Astra-Zeneca, Astro, BMS, Boehringer-Ingelheim, Celgene, Celltrion, Chugai, Gilead, Glaxo, ILTOO, Janssen, Lilly, Medimmune, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi and UCB

OP0076 Risk of developing additional immune mediated manifestations for patients with systemic arthritides

Abstract: Background Patients with the systemic arthritides ankylosing spondylitis [AS], psoriatic arthritis [PsA], rheumatoid arthritis [RA] may develop additional, non-musculoskeletal immune mediated manifestations (nms-IMMs). Objectives To compare the risk of developing nms-IMMs between patients with and without an existing AS, PsA, or RA. Methods Risk for nms-IMMs was estimated in the MarketScan Commercial Claims and Encounters database (1/2006–9/2015) for case patients with AS, PsA, RA (the “systemic arthritides”). Up to 1,000 controls were matched with replacement by age, sex, state of residence and insurance type to case patients aged 18–64. The systemic arthritides (“cases”) were identified by ICD-9 diagnosis codes on ≥2 medical claims ≥30 days apart. A case patient9s earliest nms-IMM claim was designated as the index date for the case and all matched controls. Onset of 6 nms-IMDs was identified by the first post-index claim: celiac disease [CE], hidradenitis suppurativa [HS], inflammatory bowel disease [IBD], lupus [SLE], psoriasis [PsO], uveitis [UV]; some of these are well-known manifestations of seronegative spondylarthropathies, like PsA and AS; some are not. All subjects had continuous health plan enrollment for ≥365 days before and after index date. Cumulative incidence of nms-IMMs was assessed at 5 years. Their risk was analyzed with stratified Cox proportional hazards models. Standard errors were adjusted for clustering by case-control match group. Results Among 117,794 cases, mean age was 49 years and 71% were female. Mean number of matched controls per case was 664. Across the 3 initial cohorts of patients with AS, PsA, or RA, median follow-up ranged 939–972 days for cases and 931–950 days for controls. Among case patients, 5-year cumulative incidence of any nms-IMM occurrence was 17.5% for AS, 41.8% for PsA, and 14.4% for RA. Patients with nms-IMMs had significantly higher risk than matched controls of developing each, any 1, or any 2 of the 6 manifestations (P≤0.002) (Table). Conclusions The risk of developing non-musculoskeletal manifestations was significantly higher for patients with AS, PsA, and RA than for matched controls. These included not only the well-known manifestations of PsA and AS but also others like manifestations leading to claims for SLE, celiac disease or HS. When managing these systemic arthritides, surveillance for additional immune mediated manifestation is warranted. Acknowledgements Design, study conduct, and financial support for the study were provided by AbbVie Inc. AbbVie participated in the interpretation of data, review, and approval of the abstract; all authors contributed to the development of the abstract and maintained control over the final content. Medical writing services were provided by Andrew Epstein of Medicus Economics and were funded by AbbVie. Disclosure of Interest D. Aletaha Grant/research support from: AbbVie, AstraZeneca, BMS, Eli Lilly, Grunenthal, Jansen, Medac, Merck, Mitsubishi Tanabe, Novo Nordisk, Pfizer, and Sanofi/Regeneron, Consultant for: AbbVie, AstraZeneca, BMS, Eli Lilly, Grunenthal, Jansen, Medac, Merck, Mitsubishi Tanabe, Novo Nordisk, Pfizer, and Sanofi/Regeneron, Speakers bureau: AbbVie, AstraZeneca, BMS, Eli Lilly, Grunenthal, Jansen, Medac, Merck, Mitsubishi Tanabe, Novo Nordisk, Pfizer, and Sanofi/Regeneron, R. Panaccione Consultant for: AbbVie, Amgen, AstraZeneca, Axcan Pharma (now Aptalis), Biogen Idec, Bristol-Myers Squibb, Centocor, ChemoCentryx, Eisai Medical Research Inc, Elan Pharmaceuticals, Ferring, Genentech, GlaxoSmithKline, Janssen, Merck Sharp & Dohme Corp, Millennium Pharmaceuticals Inc (now Takeda), Ocera Therapeutics Inc, Otsuka America Pharmaceutical, Pfizer, Shire Pharmaceuticals, Prometheus Laboratories, Schering-Plough Corporation, Synta Pharmaceuticals Corp, Teva, UCB Pharma, and Warner Chilcott, Speakers bureau: AbbVie, Amgen, AstraZeneca, Axcan Pharma (now Aptalis), Biogen Idec, Bristol-Myers Squibb, Centocor, ChemoCentryx, Eisai Medical Research Inc, Elan Pharmaceuticals, Ferring, Genentech, GlaxoSmithKline, Janssen, Merck Sharp & Dohme Corp, Millennium Pharmaceuticals Inc (now Takeda), Ocera Therapeutics Inc, Otsuka America Pharmaceutical, Pfizer, Shire Pharmaceuticals, Prometheus Laboratories, Schering-Plough Corporation, Synta Pharmaceuticals Corp, Teva, UCB Pharma, and Warner Chilcott, M. Davis Employee of: Medicus, which has received payment from AbbVie to assist with data analysis, S. Johnson Employee of: Medicus, which has received payment from AbbVie to assist with data analysis, M. Skup Shareholder of: AbbVie, Employee of: AbbVie, V. Garg Shareholder of: AbbVie, Employee of: AbbVie