Objective: Characterize psoriatic arthritis (PsA) heterogeneity and develop a conceptual framework to model the clinical and economic value of treatments on key PsA disease domains. Methods: We performed a narrative literature review to identify the key PsA disease domains and outcome measures for these and explore the existing evidence base of clinical and economic evaluations of current PsA treatments on key disease domains. We propose an economic modelling framework that could estimate the economic value of PsA treatments on disease domains. Results: Our literature review identified the following key PsA disease domains: peripheral arthritis, dactylitis, enthesitis, psoriatic spondylitis, skin, and nail lesions, and associated key outcome measures. Our review of the literature, including clinical guidelines, suggests that the evidence base of specific treatment performance on modulating outcomes for a given domain was not strong. We propose an economic modelling framework to estimate the economic value of treatments for addressing specific PsA disease domains. Given existing evidence gaps, we would recommend a cohort-level model with a lifetime horizon, to estimate total social value as well as the cost per outcome and change in cost per symptom avoided. The significant patient heterogeneity in PsA would suggest an individual/patient-level simulation but is likely not feasible with existing data. Conclusions: PsA is a heterogeneous disease, with a number of key disease domains and variable presentation. A better understanding of the performance of treatments on given disease domains would help support patients, providers, payers, HTA's, and health care policy makers in making personalized treatment decisions.

Background Current rheumatoid arthritis (RA) treatment guidelines recommend the use of disease activity measures (DAMs) to guide RA therapy. These guidelines recommend considering escalation of therapy in RA patients with high or moderate disease activity. Recent work by our group has demonstrated that many RA patients with high/moderate RA by Disease Activity Score with 28 joints (DAS28) did not have therapy escalated despite active disease (DAS28 ≥3.2). Objectives 1) To determine if the rate of major therapeutic change (MTC) for RA patients with high/moderate disease activity based on DAS28 was similar when measured using two other common DAMs; 2) to compare the ability of different DAMs to predict MTC across the full spectrum of RA disease activity. Methods US Veterans enrolled in the VA Rheumatoid Arthritis (VARA) registry with 1) a complete set of DAMs (DAS28, Clinical Disease Activity Index [CDAI], Routine Assessment of Patient Index Data 3 [RAPID3]) recorded (index date), 2) two other visits during the preceding 18 months separated by at least 60 days, and 3) clinical data available for 18 months prior to through 30 days following index date were eligible. Each patient was assessed for MTC within 1 week before and 30 days after index date. MTC was defined as any of the following: 1) initiation of new biologic or nonbiologic DMARD, 2) escalation of DMARD dose by ≥25%, 3) initiation of prednisone (as new agent or after 90 day gap during baseline), or 4) increase in monthly average prednisone dose by 25% and/or 5) injection of 2 or more joints with corticosteroids. MTC was analysed by DAM severity thresholds of 1) high, moderate, low, and remission, and 2) high, high/moderate, and high/moderate/low levels. Analyses of the latter thresholds included sensitivity, specificity, predictive values, and accuracy estimations for MTC at each DAM level. Results Of 1776 eligible patients, 89% were male, mean age was 63.4 years, mean disease duration was 13.4 years, 79% tested positive for rheumatoid factor, and 63% positive for anti-cyclic citrullinated peptide antibodies. Overall, 33.1% (591/1776) of patients had an MTC. A markedly larger percentage of patients with high disease activity had MTC (range 55.1%–43.5%) compared to patients with moderate disease (range 38.7%–27.8%) (table 1). Sensitivity, specificity, predictive values, and accuracy at each DAM threshold level varied markedly by DAM, with RAPID3 having a higher sensitivity, lower specificity, and less accuracy than DAS28 or CDAI (table 2).Abstract FRI0018 – Table 1 Rates of MTC Stratified by DAMAbstract FRI0018 – Table 2 Performance of DAMs for Prediction of MTC Conclusions Most patients with high/moderate disease activity did not have a MTC. This observation was consistent regardless of which DAM was utilised. MTC increased with disease activity with all DAMs; however, DAS28 and CDAI appeared to have greater accuracy than RAPID3 at predicting MTC at all disease severity thresholds. There is need for continued evaluation of DAM thresholds for defining disease activity for MTC decisions, better DAMs, and/or better application of DAMs in clinical practice to improve the treatment of patients with active RA. Acknowledgements This study was sponsored by Immunex, a subsidiary of Amgen. Medical writing assistance provided by Amgen. Disclosure of Interest G. Cannon Grant/research support from: Amgen, C.-C. Teng Grant/research support from: Amgen, N. Accortt Shareholder of: Amgen, Employee of: Amgen, D. Collier Shareholder of: Amgen, Employee of: Amgen, T.-C. Lin Shareholder of: Amgen, Employee of: Amgen, B. Sauer Grant/research support from: Amgen Inc.

Objective To examine factors associated with major therapeutic changes (MTC) among US Veterans with moderate/severe rheumatoid arthritis (RA) based on Disease Activity Score based on 28 joints (DAS28). Methods We used data from patients enrolled in the Veterans Affairs Rheumatoid Arthritis (VARA) registry from 1/1/2006 through 12/31/2014. The index date was a clinic visit with DAS28 > 3.2 (moderate/severe disease) following an 18-month pre-index period that included >= 2 DAS28 measurements >= 60 days apart. The patients were followed for MTC from 7 days pre-index through 90 days post-index. Poisson multivariable regression models were used to identify associations with MTC. Chart review of a subset of randomly selected patients explored factors that impacted therapeutic decisions. Results Among 941 patients, 396 (42.1%) had MTC. Of these, 369 (39.2%) patients had worsening DAS28 at index, 118 (12.5%) had DAS28 improvements, and 454 (48.2%) patients had no change in DAS28 versus pre-index DAS28. Of the patients with worsening DAS28, no change in DAS28, and improved DAS28, respectively, 50.5%, 62.6%, and 70.3% had no MTC. Regression analyses showed index DAS28, oral steroid or non-biologic disease-modifying anti-rheumatic drug (nbDMARD) use in the previous year were associated with an increased likelihood of MTC; use of nbDMARDs in the previous 90 days was associated with a decreased likelihood of MTC. The most common reason for not modifying therapy despite DAS28 > 3.2 was a judgement of mild disease. Conclusion Clinicians frequently do not institute major therapeutic changes despite DAS28 indicating moderate/severe disease activity; multiple factors are involved in real-world treatment decisions.

Background PsA patients have greater prevalence of cardiovascular disease (CVD), metabolic syndrome (MetS), and cancer than patients without PsA. Objectives To examine patient characteristics and disease activity by comorbidity profile among PsA patients. Methods This analysis included adults with PsA enrolled in the US Corrona PsA/spondyloarthritis Registry from March 2013-March 2017 and followed for ≥6 months. Prevalence (at registry entry) and incidence rate (time to new events after registry entry) of CVD, MetS, and cancer were determined. Patient characteristics and disease activity were described by prevalent comorbidity, with t-tests for means despite skewed data and chi-squared tests for percentages. Results The analysis included 1493 patients and 3564 patient-years of follow-up. Incidences (95% confidence interval) per 1000 patient-years were 9.4 (6.5–13.5), 1.0 (0.3–3.1), and 11.4 (8.2–15.8) for CVD, MetS, and cancer (6.8 [4.5–10.2] nonmelanoma skin cancer), respectively. PsA patients with (vs without) prevalent CVD, MetS, or cancer were older, and fewer had full-time jobs or private insurance. Patients with (vs without) CVD had higher swollen joint count and mean body surface area, and tended to have higher rates of obesity. Patients with (vs without) MetS tended to have greater disease activity. Patients with (vs without) comorbidities reported less disease activity on patient global assessment. Data are mean or% a≥3 of 4 conditions: hypertension, hyperlipidemia, diabetes mellitus, or obesity bP value across all categories for employment or body mass index Conclusions PsA patients with (vs without) CVD had greater disease activity and those with (vs without) MetS tended to have greater disease activity by physician-derived measures, but PsA patients with (vs without) CVD or MetS reported lower global assessment of disease activity. Patient perception of PsA may mask the effect of comorbid CVD or MetS on disease activity. Acknowledgements Amgen Inc. supported this work. Corrona has been supported by AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, BMS, Crescendo, Eli Lilly and Company, Genentech, GSK, Horizon Pharma USA, Janssen, Momenta Pharmaceuticals, Novartis, Pfizer, Roche, and UCB. Jonathan Latham (PharmaScribe) and Linda Rice (Amgen) provided medical writing support. Disclosure of Interest P. Mease Grant/research support from: Abbvie, Amgen, Bristol Myers Squibb, Janssen, Lilly, Novartis, Pfizer, Sun, UCB, Consultant for: Abbvie, Amgen, Bristol Myers Squibb, Janssen, Lilly, Merck, Novartis, Pfizer, Sun, UCB, Zynerba, Speakers bureau: Abbvie, Amgen, Bristol Myers Squibb, Genentech, Janssen, Novartis, Pfizer, UCB, H. Litman Employee of: Corrona, LLC, N. Accortt Shareholder of: Amgen Inc., Employee of: Amgen Inc., S. Rebello Employee of: Corrona, LLC, J. Greenberg Shareholder of: Corrona, LLC, Consultant for: Genentech, Janssen, Pfizer, Eli Lilly, Novartis, Employee of: Corrona, LLC, H. Feng Employee of: Corrona, LLC, M. Gharaibeh Shareholder of: Amgen Inc., Employee of: Amgen Inc., G. Aras Shareholder of: Amgen Inc., Employee of: Amgen Inc., D. Collier Shareholder of: Amgen Inc., Employee of: Amgen Inc.

Background Until recently, treatment for moderate to severe psoriatic arthritis (PsA) mainly focused on conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and tumour necrosis factor inhibitors (TNFis). However, the persistence of TNFis alone or in combination with csDMARDs is not well understood. Objectives To assess real-word treatment patterns among patients with PsA receiving TNFi monotherapy, csDMARD monotherapy, or TNFi and csDMARD combination therapy. Methods This retrospective study utilised data from patients with PsA aged ≥18 years, enrolled in the Corrona PsA registry between March 21, 2013, and July 31, 2017, treated with a TNFi and/or csDMARD (index therapy), and with ≥6 months of follow-up time. Patients were stratified by prevalent (initiation before enrollment) or incident (initiation after enrollment) therapy use; cohorts were based on index therapy: TNFi monotherapy, csDMARD monotherapy, or combination therapy. Outcomes of interest were the percentage of patients who were persistent on their index therapy or had a therapy change (discontinued, switched, or restarted) 12 months after the index visit. Results There were 1266 patients in this study: 1144 prevalent and 122 incident (table 1). Patient characteristics at the index date were similar among patients; however, csDMARD monotherapy patients had higher disease activity than either TNFi group. Among prevalent patients, TNFi monotherapy patients were likely to be female (59%) and younger (51.9 years), nearly all patients had psoriasis, and BSA was similar and ≤5. At month 12, among patients with a follow-up visit within the 9–15–month window, the vast majority of prevalent patients and half of incident patients were persistent on their index therapy, and one quarter to one third of incident patients discontinued or switched therapy (table 1). Conclusions Most patients who were prevalent on therapy at the time of enrollment in Corrona remained persistent on their therapy for 12 months in this study, while roughly half of patients initiating therapy after enrollment remained persistent over the same period. Young, female patients were more likely to receive TNFi monotherapy; the TNFi monotherapy cohort was associated with the least disease activity. The incident group was not different from the prevalent group. Although the prevalent group is more likely to have patients who responded to treatment, the data suggest that most therapy changes occur within the first year of PsA treatment. Disclosure of Interest P. Mease Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Janssen, Lilly, Novartis, Pfizer, Sun, and UCB, Consultant for: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Janssen, Lilly, Novartis, Pfizer, Sun, and UCB, Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Genentech, Janssen, Novartis, Pfizer, and UCB, N. Accortt Shareholder of: Amgen Inc., Employee of: Amgen Inc., S. Rebello Employee of: Corrona LLC, C. Etzel Consultant for: Merck, Employee of: Corrona LLC, R. Harrison Employee of: Corrona LLC, G. Aras Shareholder of: Amgen Inc., Employee of: Amgen Inc., M. Gharaibeh Shareholder of: Amgen Inc., Employee of: Amgen Inc., J. Greenberg Shareholder of: Corrona LLC, Consultant for: Genentech, Janssen, Novartis, Pfizer, and Eli Lilly, Employee of: Corrona LLC, D. Collier Shareholder of: Amgen Inc., Employee of: Amgen Inc.

BACKGROUND:Some patients with plaque psoriasis experience secondary failure of tumour necrosis factor inhibitor therapy. OBJECTIVES:To evaluate efficacy, safety and patient-reported outcomes (PROs) with etanercept in patients with secondary adalimumab failure. METHODS:This phase IV open-label single-arm estimation study (NCT01543204) enrolled patients on adalimumab who had achieved static Physician's Global Assessment (sPGA) score 0/1 (clear/almost clear). Patients subsequently lost response, defined as sPGA ≥ 3 or loss of 50% improvement in Psoriasis Area and Severity Index (PASI 50). At baseline, patients had involved body surface area ≥ 10%, sPGA ≥ 3 and PASI ≥ 10. Antiadalimumab antibodies (ADAs) were measured at screening. Patients received etanercept 50 mg twice weekly for 12 weeks, followed by 50 mg weekly. The primary end point was sPGA 0/1 at week 12 (intention-to-treat analysis; no hypothesis tested). Additional outcomes included rates of sPGA 0/1, PASI responses, safety, PROs of itch, pain and flaking, Dermatology Life Quality Index, treatment satisfaction and Work Productivity and Activity Impairment questionnaire. RESULTS:Sixty-four patients enrolled; 67% had ADAs. sPGA 0/1 rates at week 12 were 39·7% [95% confidence interval (CI) 27·6-52·8; primary end point] and 45% (95% CI 29·3-61·5) for patients positive for ADAs and 35% (95% CI 15·4-59·2) for patients negative for ADAs. PASI 75 response rates at week 12 were 47·5% (95% CI 31·5-63·9) for patients who were positive for ADAs and 50% (95% CI 27·2-72·8) for patients negative for ADAs. No new safety signals were observed. PROs of itch, pain and flaking consistently improved at week 12 and were maintained through week 24. CONCLUSIONS:Patients with psoriasis who experienced secondary failure of adalimumab achieved satisfactory response to etanercept regardless of ADA status.

Background Administrative claims contain detailed medication, diagnosis, and procedure data, but their lack of clinical outcomes for RA has limited their use in comparative effectiveness research. A validated claims-based algorithm uses a combination of adherence, dosing, and treatment modifications to estimate biologics’ clinical effectiveness as proxies for low disease or remission for RA.1 In the validation study, “effectiveness” was defined as reaching DAS 28 low disease activity or remission one year after initiating treatment. Objectives To implement this algorithm in a US managed-care database and calculate the cost per effectively treated patient among biologics approved for moderate to severe RA (etanercept, adalimumab, infliximab, golimumab, and abatacept). Methods Data were obtained from the commercially insured cohort in the Truven Marketscan Database. The cohort included patients with RA aged 18-63, initiating treatment between January 2007 and December 2010, without biologics 6 months before their first (index) treatment in the database, and continuously enrolled 6 months before and 12 months after their index biologic. Other disease indications for TNF therapy were excluded. The algorithm defines lack of effectiveness as: medication possession ratio < 80% (or fewer infusions/injections than specified on US label), increase in biologic dose or frequency interval, switching biologics, adding new non-biologic Disease Modifying Anti-Rheumatic Drugs, glucocorticoid, dose increase or initiation, or more than one parenteral or intra-articular glucocorticoid injection during follow-up. Drug and administration costs were obtained from allowed amounts on claims. Cost per effectively treated patient was calculated as total drug cost for all patients initiating treatment on a given agent divided by the number of patients in whom that agent was classified as “effective” by the algorithm. Results The cohort included 15,351 patients, with a mean age of 49.7 (SD 9.5) years and 78.3% were female. Algorithm effectiveness criteria were met in 30% of etanercept (n=6,374), 30% of adalimumab (n=4,661), 20% of infliximab (n=2,765), 27% of abatacept (n=1,338), and 29% of golimumab (n=213) patients in the first 12 months of treatment. Mean first year cost per “effectively treated patient” was lowest for etanercept ($49,952), followed by golimumab ($50,189), adalimumab ($52,858), abatacept ($71,866), and infliximab ($104,333). Conclusions Algorithm-defined effectiveness was similar for all agents other than infliximab. Cost per “effectively treated patient” was lower for self-injected than infused biologics using a new, validated claims-based algorithm. References Curtis JR. et al. Derivation and preliminary validation of an administrative claims-based algorithm for the effectiveness of medications for rheumatoid arthritis. Arthritis Res Ther. 13:R155, 2011 Acknowledgements Research funded by Immunex Corporation, a wholly owned subsidiary of Amgen Inc., and by Wyeth, which was acquired by Pfizer Inc. in October 2009. Disclosure of Interest J. Curtis Grant/research support from: Roche/Genentech, UCB, Centocor, CORRONA, Amgen, Pfizer BMS, Janssen, AbbVie, V. Schabert: None Declared, J. Yeaw: None Declared, J. Korn: None Declared, C. Quach Consultant for: Amgen, Inc., D. Harrison Shareholder of: Amgen Inc., Employee of: Amgen, Inc., H. Yun: None Declared, G. Joseph Shareholder of: Amgen, Inc., Pfizer Inc., Employee of: Amgen, Inc., D. Collier Shareholder of: Amgen, Inc., Employee of: Amgen, Inc.

Background Comparison of adalimumab (ADA), etanercept (ETN), and infliximab (INF) use in clinical practice may provide important insight into the comparative effectiveness and cost of approved therapies. Objectives To examine persistence, dose escalation, clinical outcomes, and treatment costs with ADA, ETN, and INF for patients (pts) enrolled in the US Veterans Affairs RA (VARA) registry. Methods VARA links to VA pharmacy and administrative databases, and documents longitudinal assessments of disease activity and outcomes. VARA pts initiating ADA, ETN, or INF from 3/18/2003 to 9/30/2010 were identified with follow-up data collected for ≥12 months. This analysis was limited to first treatment course beginning ≥180 days after VARA enrollment. A treatment course was defined as continuous medication dispensing in the absence of ≥90-day gap. Dose escalation was ≥25% increase in weekly dose. Cost was determined by drug costs alone and including drug administration (dispensing/infusion costs). Results Data from 563 pts (204 ADA; 290 ETN; 69 INF) were analyzed (Table). No differences in persistence were seen (Fig A). Dose escalation was most common with INF followed by ADA (Fig B). Persistence post-escalation was similar for all agents. Mean DAS28 and change in DAS28 in 61 evaluable pts were similar for each drug. Average annual costs were highest for INF. Image/graph: Conclusions In VARA, persistence on ADA, ETN and INF was similar. Escalation was most common with INF and least frequent with ETN, and did not impact persistence. Drug costs were higher for INF than ADA and ETN. Persistence and DAS scores were similar regardless of dose escalation. Acknowledgements Research funded by VA Research Program and Immunex Corporation, a wholly owned subsidiary of Amgen Inc., and by Wyeth, which was acquired by Pfizer Inc. in October 2009. Disclosure of Interest G. Cannon Grant/research support from: Amgen Inc., S. DuVall Grant/research support from: Amgen Inc, Anolinx LLC, Genentech Inc, F. Hoffmann-La Roche Ltd, Merck & Co Inc, Mylan Specialty LP, and Shire PLC, C. Hayden: None Declared, L. Caplan: None Declared, J. Curtis Grant/research support from: Roche/Genentech, UCB, Centocor, CORRONA, Amgen, Pfizer BMS, Janssen, AbbVie, K. Michaud: None Declared, T. Mikuls Grant/research support from: Genentech/Roche, A. Reimold Grant/research support from: Lilly, Novartis, Janssen, Ardea, Consultant for: UCB, D. Collier Shareholder of: Amgen Inc., Employee of: Amgen Inc., D. Harrison Shareholder of: Amgen Inc., Employee of: Amgen Inc., G. Joseph Shareholder of: Amgen Inc., Pfizer Inc., Employee of: Amgen Inc., B. Sauer Grant/research support from: Amgen Inc.

Background Tumor necrosis factor (TNF)-blockers are effective in treating RA, but the benefit of switching between TNF-blockers is less clear. Objectives To examine switching, costs and factors associated with switching between adalimumab (ADA), etanercept (ETN), and infliximab (INF) in patients (pts) in the Veterans Affairs Rheumatoid Arthritis (VARA) registry following their first VA episode of TNF-blocker use. Methods VARA is a longitudinal, observational, cohort study of US veterans with RA. It links to VA pharmacy and administrative data and documents longitudinal assessments of RA disease activity and outcomes. VARA patients initiating ADA, ETN, or INF from March 2003 to Sept 2010 were identified and followed until Sept 2011. A treatment course was defined as continuous TNF-blocker use without ≥90-day gap. Cost of TNF-blockers with and without drug administration costs was determined for first and second courses. Results Data from 563 RA pts (204 ADA, 290 ETN, 69 INF) initiating therapy were analyzed. During observation (5.2±2.1 years), 47% had a single TNF-blocker course, 25% restarted the same TNF-blocker and 28% switched. Patients with a single course were older than pts with multiple courses. In the 61 pts with pre- and post-treatment DAS28, pts who switched had higher DAS28 on treatment than pts restarting the same TNF-blocker. DAS28 was similar before and after the second TNF-blocker course in both groups. Patients with ≥25% increase in dose or ETN as initial therapy were more likely to switch. In pts who switched, initial annualized costs were numerically higher in the first course and statistically significantly higher during the second course than for pts who restarted their TNF-blocker. Conclusions In VARA, approximately 50% of pts had at least 1 course of TNF-blocker treatment. Patients who switched had higher DAS28 scores during the initial course, a history of dose escalation with the initial agent and higher costs. Due to potential confounding factors inherent in observational studies, more research is needed to understand reasons for switching and the effects of switching TNF-blockers on overall outcomes in RA. Acknowledgements Research funded by VA Research Program and Immunex Corporation, a wholly owned subsidiary of Amgen Inc., and by Wyeth, which was acquired by Pfizer Inc. in October 2009. Disclosure of Interest G. Cannon Grant/research support from: Amgen, S. DuVall Grant/research support from: Amgen, Anolinx LLC, Genentech, F. Hoffman-LaRoche Ltd, Merck & Co, Mylan Specialty LP, Shire PLC, C. Hayden: None Declared, L. Caplan: None Declared, J. Curtis Grant/research support from: Roche/Genentech, UCB, Centocor, CORRONA, Amgen, Pfizer BMS, Janssen, AbbVie, K. Michaud Employee of: National Databank of Rheumatic Diseases, Wichita, KS, T. Mikuls Grant/research support from: Genentech/Roche, A. Reimold Grant/research support from: Lilly, Novartis, Janssen, Ardea, Consultant for: UCB, D. Collier Shareholder of: Amgen, Employee of: Amgen, G. Joseph Shareholder of: Amgen, Pfizer, Employee of: Amgen, D. Harrison Shareholder of: Amgen, Employee of: Amgen, B. Sauer Grant/research support from: Amgen

Background The efficacy of etanercept (ETN), alone or in combination with the disease-modifying antirheumatic drug (DMARD) methotrexate (MTX), has been demonstrated in randomized clinical trials (RCTs) of patients with rheumatoid arthritis (RA). RCTs are conducted in select patient (pt) populations, and thus it is important to determine how findings from RCTs compare with clinical practice. Objectives To compare remission rates among pts with RA initiating ETN therapy in routine clinical practice settings in the Rheumatoid Arthritis DMARD Intervention and Utilization Study (RADIUS II, a prospective observational study) with remission rates in the Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes (TEMPO, a double-blind RCT). Methods Pt demographics, baseline characteristics, disease activity over time, remission status, and time to remission were evaluated for pts initiating ETN (monotherapy or ETN+MTX). Continued remission (Clinical Disease Activity Index [CDAI] of ≤2.8 for ≥6 months with at least two observations within a continuous observation period) was determined through year 3 by treatment group and study. The remission rate was determined for differing levels of disease severity. Results In TEMPO, 223 patients started ETN alone and 231 pts started ETN+MTX simultaneously. In RADIUS II, 1172 pts initiated ETN monotherapy and 2376 pts added ETN to established MTX (ETN+MTX). Pts in RADIUS II had lower disease activity at baseline (mean [SD] CDAI: 36 [13]) than those in TEMPO (CDAI: 47 [13], P<0.001). Most other clinical and demographic features (eg, age, rheumatoid factor, sex) were comparable at baseline. In each study, likelihood for CDAI remission and time to remission varied with baseline disease activity (Table 1). Generally, more patients with lower baseline CDAI scores achieved remission by year 3 in both trials than those with higher baseline CDAI scores (Table 1). There was a more rapid onset of CDAI remission in TEMPO than RADIUS II that may be explained in part by compliance, other pt differences, or in the case of combination therapy, simultaneous (rather than sequential) initiation of ETN+MTX. Conclusions ETN, with or without MTX, effectively induced remission by year 3 in routine clinical practice as seen in a RCT. Pts with lower disease severity were more likely to reach remission. Differences in drug initiation sequence might limit the ability to compare ETN+MTX groups in RCTs versus real world. These analyses indicate that continued remission may be more likely in pts who reached remission earlier. Disclosure of Interest E. Keystone Grant/Research support from: Immunex Corp, a wholly owed subsidiary of Amgen Inc; Wyeth, which was acquired by Pfizer in Oct 2009, G. Cannon Grant/Research support from: Immunex Corp, a wholly owed subsidiary of Amgen Inc; Wyeth, which was acquired by Pfizer in Oct 2009, B. Wang: None Declared, G. Park Shareholder of: Amgen Inc, Employee of: Amgen Inc, A. Koenig Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, D. Collier Shareholder of: Amgen Inc, Employee of: Amgen inc

OBJECTIVE:This study compares the responsiveness to change of the Medical Outcomes Study Short Form Health Survey (SF-36), a measure of health related quality of life (HRQOL), and the Health Assessment Questionnaire Disability Index (HAQ-DI), a function instrument, in a randomized clinical trial for treatment of systemic sclerosis (SSc). METHODS:A phase 2/3, multicenter, prospective, placebo controlled trial was conducted to evaluate human recombinant relaxin treatment in patients with diffuse SSc over 24 weeks. At baseline, subjects had stable, moderately severe, diffuse SSc of disease duration < or = 5 years, modified Rodnan skin score > or = 20, serum creatinine < 2.0 mg/dl, percentage forced vital capacity (% FVC) predicted > or = 50%, and % DLCO predicted > or = 40% and were not receiving concomitant disease modifying therapies. Internal consistency reliability of multi-item scales was estimated using Cronbach's alpha. Responsiveness to change of the SF-36 and HAQ-DI was computed between Weeks 0 and 24. Subjects were classified as unchanged or having a meaningful change in 4 different external measures: Change in (1) skin score > or = 30%; (2) % FVC predicted of > or = 15%; (3) self-reported patient global assessment by visual analog scale (VAS) > or = 20%; and (4) physician global assessment by VAS of > or = 20%. Responsiveness indices were computed and Cohen's effect size criteria were used to assess the magnitude of change. RESULTS:A total of 239 patients participated in this trial, with 196 completing the 24 week trial. Cronbach's alpha for the SF-36 scales ranged from 0.76 to 0.93 and for the HAQ-DI ranged from 0.69 to 0.91 (good to excellent). The SF-36 had a larger magnitude of responsiveness in overall disease (patient and physician global assessment) compared to the HAQ-DI, while the HAQ-DI had a larger magnitude of responsiveness in clinical measures (i.e., change in skin score and % FVC predicted) than the SF-36. CONCLUSION:These data support inclusion of both the SF-36 and HAQ-DI as outcome measures in future clinical trials of diffuse SSc.

OBJECTIVETo document disease activity and functional status in patients with scleroderma (systemic sclerosis [SSc]) and Raynaud's phenomenon (RP) and to determine the sensitivity to change, reliability, ease of use, and validity of various outcome measures in these patients.METHODSPatients with SSc and moderate-to-severe RP participating in a multicenter RP treatment trial completed daily diaries documenting the frequency and duration of RP attacks and recorded a daily Raynaud's Condition Score (RCS). Mean scores for the 2-week periods prior to baseline (week 0), end of trial (week 6), and posttrial followup (week 12) were calculated. At weeks 0, 6, and 12, physicians completed 3 global assessment scales and performed clinical assessments of digital ulcers and infarcts; patients completed the Health Assessment Questionnaire (HAQ), the Arthritis Impact Measurement Scales 2 (AIMS2) mood and tension subscales, 5 specific SSc/RP-related visual analog scales (VAS), and 3 other VAS global assessments. We used these measures to document baseline disease activity and to assess their construct validity, sensitivity to change, and reliability in trial data.RESULTSTwo hundred eighty-one patients (248 women, 33 men; mean age 50.4 years [range 18-82 years]) from 14 centers participated. Forty-eight percent had limited cutaneous SSc; 52% had diffuse cutaneous SSc. Fifty-nine patients (21%) had digital ulcers at baseline. Patients had 3.89 +/- 2.33 (mean +/- SD) daily RP attacks (range 0.8-14.6), with a duration of 82.1 +/- 91.6 minutes/attack. RCS for RP activity (possible range 0-10) was 4.30 +/- 1.92. HAQ scores (0-3 scale) indicated substantial disability at baseline (total disability 0.86, pain 1.19), especially among the subscales pertaining to hand function (grip, eating, dressing). AIMS2 mood and tension scores were fairly high, as were many of the VAS scores. Patients with digital ulcers had worse RCS, pain, HAQ disability (overall, grip, eating, and dressing), physician's global assessment, and tension, but no significant difference in the frequency of RP, duration of RP, patient's global assessment, or mood, compared with patients without digital ulcers. VAS scores for digital ulcers as rated by the patients were not consistent with the physician's ratings. Factor analysis of the 18 measures showed strong associations among variables in 4 distinct domains: disease activity, RP measures, digital ulcer measures, and mood/tension. Reliability of the RCS, HAQ pain and disability scales, and AIMS2 mood and tension subscales was high. The RP measures demonstrated good sensitivity to change (effect sizes 0.33-0.76).CONCLUSIONOur findings demonstrate that the significant activity, disability, pain, and psychological impact of RP and digital ulcers in SSc can be measured by a small set of valid and reliable outcome measures. These outcome measures provide information beyond the quantitative metrics of RP attacks. We propose a core set of measures for use in clinical trials of RP in SSc patients that includes the RCS, patient and physician VAS ratings of RP activity, a digital ulcer/infarct measure, measures of disability and pain (HAQ), and measures of psychological function (AIMS2).

OBJECTIVE To evaluate the efficacy and tolerability of an oral preparation of iloprost, a prostacyclin analog, in patients with Raynaud's phenomenon (RP) secondary to systemic sclerosis (scleroderma). METHODS A multicenter, randomized, parallel-group, placebo-controlled double-blind study was performed at university and community-based medical centers. Patients were randomly assigned to receive either 50 microg of iloprost orally twice daily or an identical gelatin-coated capsule containing placebo for 6 weeks. Outcome measures included average total daily duration of RP attacks, average number of RP attacks, and RP condition scored via a standardized daily diary. RESULTS Three hundred eight patients with scleroderma (272 women, 36 men, mean age 49 years [range 18-80]) were enrolled. One hundred fifty seven were assigned to receive iloprost and 151 to receive placebo. One hundred forty-three patients in the iloprost group (91.1%) and 144 in the placebo group (95.4%) completed the 6-week treatment phase. Fifteen of these treated patients (8 iloprost, 7 placebo) failed to complete all of the followup visits. The mean reduction in the average duration of attacks from baseline to week 5-6 was 24.32 minutes in the iloprost group and 34.34 minutes in the placebo group (P = 0.569). Likewise, the mean reduction from baseline to week 5-6 in the daily frequency of attacks was 1.02 in the iloprost group and 0.83 in the placebo group (P = 0.459). The Raynaud's condition score, a patient-completed assessment of the severity of RP attacks, was reduced by 1.32 in the iloprost group and 1.00 in the placebo group (P = 0.323). The lack of significant difference between treatment groups did not change when a variety of factors, including use of other vasodilators, duration of disease, classification of scleroderma (limited versus diffuse), or number of baseline digital ulcers were taken into account. Premature withdrawal from the study due to adverse events occurred in 10 patients (6.4%) in the iloprost group and 3 (2.0%) in the placebo group (P = 0.058). CONCLUSION Oral iloprost at a dosage of 50 microg twice daily is no better than placebo for management of RP secondary to scleroderma, either during 6 weeks of treatment or during 6 weeks of posttreatment followup.

OBJECTIVEUsing data from 3 independent studies, to quantify the interobserver reliability of semi-quantitative skin scoring methods (the original and the modified Rodnan skin thickness scores) used to assess the degree and extent of cutaneous thickening in systemic sclerosis (SSc).METHODInterobserver variability of the original Rodnan skin thickness score method (cutaneous thickness assessed in 26 body surface areas using a 0-4 scale) was evaluated in one study. The modified Rodnan method (cutaneous thickness assessed in 17 body surface areas using a 0-3 scale) was evaluated in 2 studies. In all 3 studies, each patient's skin thickness was assessed by 6 or 7 observers in a blinded fashion.RESULTSThe overall within patient standard deviations were not statistically different in all 3 studies (5.4, 4.6 and 4.6) irrespective of the overall mean skin thickness scores (26.6, 18.3 and 17.7). With the original Rodnan technique, the within patient standard deviation tended to be higher in patients with higher skin thickness scores. In the 2 studies which used the modified technique, no significant differences in within patient standard deviation were noted between high and low skin thickness scores.CONCLUSIONSThree independent studies demonstrate that the Rodnan skin thickness scoring techniques are reproducible among different observers (the within patient standard deviation being consistently about 5 units). Our data provide valuable information needed for sample size calculations for SSc trials in which skin thickness score is an outcome variable.