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Background This retrospective study gathered medical/pharmacy claims data on patients with IBD between 01/01/2000 and 03/31/2019 from the IBM® MarketScan® commercial claims database to assess the real-world impact of fatigue on healthcare costs in patients newly diagnosed with inflammatory bowel disease (IBD). Methods Eligible participants were ≥18 years, newly diagnosed with IBD (≥2 separate claims) and had ≥12 months of continuous database enrollment before and after fatigue diagnosis. The date of fatigue diagnosis was the index date; participants were followed for 12 months post-index. Patients with (cases) or without (controls) fatigue were matched 1:1 by propensity score matching. Patients with evidence of prior IBD diagnosis/treatment, or those with a chronic disease other than IBD wherein fatigue is the primary symptom, were excluded. Healthcare resource utilization (HCRU), including hospitalizations, inpatient and outpatient visits, and associated costs was compared between cases and controls. Results Matched IBD cohorts (21,321 cases/21,321 controls) were identified (42% CD and 58% UC) with similar baseline characteristics (average age: 46 years; 60% female). Cases versus controls had significantly more all-cause outpatient visits (incidence rate ratio [IRR], 95% confidence intervals [95% CI]: 1.64 [1.61, 1.67], P Conclusions Presence of fatigue is associated with an increase in HCRU and total medical costs among patients newly diagnosed with IBD.

Introduction Our aim was to evaluate patient adherence and persistence with citrate-free adalimumab (ADA-CF), introduced in 2018 to reduce injection-site pain, compared with citrate-containing adalimumab (ADA-C). Methods This was a retrospective cohort study using a US claims database (IBM® MarketScan® Commercial and Medicare Supplemental Claims Database) from February 2018 to January 2020. Patients at least 18 years of age who were naïve to adalimumab 6 months before the index date (date of first adalimumab claim) and with at least 12 months of continuous medical and pharmacy coverage were eligible for the study. Adherence was assessed by determining the proportion of days covered (PDC) and the percentage of patients with PDC ≥ 80% during the 12-month follow-up period. Persistence was evaluated by measuring the rate of discontinuation and days to discontinuation (i.e., time on treatment) from the index date over the 12-month follow-up period. Continuous adherence outcomes (PDC) were evaluated using linear regression models. Binary adherence outcomes (PDC ≥ 80%) were assessed using logistic regression models. Kaplan–Meier analysis and Cox proportional hazards models were used to assess persistence outcomes. Results There were 2195 and 1005 patients in the ADA-CF and ADA-C cohorts, respectively, with most using adalimumab for rheumatoid arthritis (ADA-CF 29.7%, ADA-C 27.2%) and psoriasis (ADA-CF 24.5%, ADA-C 31.9%). Significantly greater adherence was achieved with ADA-CF compared with ADA-C (mean PDC [standard deviation] 0.68 [0.30] vs 0.61 [0.32], P

Patients with diabetes are more likely to be infected with Coronavirus disease 2019 (COVID-19), and the risk of death is significantly higher than ordinary patients. Dipeptidyl peptidase-4 (DPP4) is one of the functional receptor of human coronavirus. Exploring the relationship between diabetes mellitus targets and DPP4 is particularly important for the management of patients with diabetes and COVID-19. We intend to study the protein interaction through the protein interaction network in order to find a new clue for the management of patients with diabetes with COVID-19. Diabetes mellitus targets were obtained from GeneCards database. Targets with a relevance score exceeding 20 were included, and DPP4 protein was added manually. The initial protein interaction network was obtained through String. The targets directly related to DPP4 were selected as the final analysis targets. Importing them into String again to obtain the protein interaction network. Module identification, gene ontology (GO) analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis were carried out respectively. The impact of DPP4 on the whole network was analyzed by scoring the module where it located. 43 DPP4-related proteins were finally selected from the diabetes mellitus targets and three functional modules were found by the cluster analysis. Module 1 was involved in insulin secretion and glucagon signaling pathway, module 2 and module 3 were involved in signaling receptor binding. The scoring results showed that LEP and apoB in module 1 were the highest, and the scores of INS, IL6 and ALB of cross module associated proteins of module 1 were the highest. DPP4 is widely associated with key proteins in diabetes mellitus. COVID-19 may affect DPP4 in patients with diabetes mellitus, leading to high mortality of diabetes mellitus combined with COVID-19. DPP4 inhibitors and IL-6 antagonists can be considered to reduce the effect of COVID-19 infection on patients with diabetes.

Background: Few validated instruments exist for use in hidradenitis suppurativa (HS) trials. Objectives: To develop a novel HS Investigator Global Assessment (HS-IGA) and to validate its psychometric properties. Methods: Development of HS-IGA involved discussion among stakeholders, including patients, within HISTORIC. Data from replicate phase III randomized controlled trials evaluating HS treatment were utilized. Multivariate models identified lesion type and body region as variables of importance. Classification and regression trees for ordinal responses were built. Validation included assessment of test–retest reliability, predictive validity, responsiveness and clinical meaningfulness. Results: There were 3024 unique measurements available in PIONEER I. Mean and median lesion counts by region were largely

Background Glucokinase activators (GKAs) are a novel family of glucose-lowering agents used for the treatment of type-2 diabetes mellitus. Treatment with different GKAs has been shown to reduce blood glucose levels in these patients. We compared the efficacy/safety of GKAs in patients with type-2 diabetes mellitus through a meta-analysis. Methods We searched the PubMed, Excerpt Medica Database, and Cochrane Central Register of Controlled Trials databases for articles published before December 30, 2020. We computed the weighted mean difference (WMD) and 95% confidence interval (CI) for the change from baseline to the study endpoint for GKA versus placebo treatments. Results A total of 4 articles (5 studies) were included in the meta-analysis. GKAs were associated with reductions in glycated hemoglobin levels from baseline (WMD, -0.3%; 95% CI, -0.466% to -0.134%). No significant difference between GKA and placebo treatment was observed in the results of fasting plasma glucose levels from baseline (WMD 0.013 mmol/L; 95% CI, -0.304-0.33 mmol/L). A significantly higher change in 2-hour postprandial plasma glucose (2-h PPG) levels (WMD -2.434 mmol/L; 95% CI, -3.304 to -1.564 mmol/L) was observed following GKA than placebo treatment. GKAs were associated with a higher prevalence of causing hypoglycemic events than placebo treatment (risk difference [RD], 0.06; 95% CI 0.013-0.106). GKAs had no association with the risk of developing adverse effects (RD, 0.038; 95% CI, -0.03-0.106) and serious adverse events (RD, 0.01; 95% CI, -0.004-0.023). Conclusions GKAs were more effective for postprandial blood glucose control. However, these agents showed a significantly high risk of causing hypoglycemia. Prospero registration number CRD42021220364.

Introduction Patients with rheumatoid arthritis (RA) who are treated with adalimumab (ADA) are offered a proprietary patient support program (PSP, AbbVie Care®). The main objective of this study was to examine the effectiveness of ADA on RA treatment course over time in the context of PSP utilization. Methods PASSION was a 78-week post-marketing observational study of RA patients with an insufficient response to ≥1 DMARD newly initiating ADA in routine clinical care that was conducted in Europe, Israel, Mexico, Puerto Rico, and Australia. One prior biologic DMARD was allowed. The primary endpoint was percentage of patients achieving the minimal clinically important difference (MCID; improvement of ≥0.22 compared to baseline) in Health Assessment Questionnaire (HAQ) Disability Index (HAQ-DI) at week 78. Additionally, multiple clinical and patient-reported outcomes (PROs) were evaluated over time. Patients were categorized based on their participation in the PSP: ever (PSP users) vs. never (PSP non-users). Safety events were monitored throughout the study. Results Overall, 42.8% of PSP users achieved the MCID in HAQ-DI at week 78 (improvement of at least 0.22 compared to baseline). From 1025 enrolled, 48.7% of patients were PSP users while treated with ADA. The percentage of patients achieving MCID in the HAQ-DI was higher in PSP users vs. PSP non-users (48.1 vs. 37.8%) at week 78 (p

Background Glucokinase activators are a novel family of glucose-lowering agents used for the treatment of type-2 diabetes mellitus (T2DM). Glucokinase activators blind to GK activate the enzyme allosterically. Treatment with different GKAs has been shown to reduce fasting and postprandial glucose in patients with type 2 diabetes. We compared the efficacy/safety of glucokinase activators in T2DM patients through a meta-analysis. Methods We searched PubMed, Excerpt Medica Database, and Cochrane Central Register of Controlled Trials databases for articles published before December 30, 2020. Two independent reviewers extracted the information from article. The quality of articles were assessed by 2 independent reviewers using the 5 items of scale proposed by Jadad. We computed the weighted mean difference and 95% confidence interval (CI) for a change from baseline to the study endpoint for glucokinase activators vs placebo. Egger test and Begg test were used to assess the possible publication bias caused by the tendency of published studies to be positive. Results The present meta-analysis will compare the efficacy and safety of glucokinase activators and placebo for the treatment of T2DM. Conclusions This meta-analysis will provide advanced evidence on the efficacy and safety of glucokinase activators for the treatment of T2DM. Ethics and dissemination Ethical approval and patient consent are not required because this study is a literature-based study. This systematic review and meta-analysis will be published in a peer-reviewed journal. Prospero registration number CRD42021220364.

Although adalimumab (ADA) has been shown to induce and maintain clinical remission in moderate to severe ulcerative colitis (UC), some patients (pts) may lose initial response and could benefit from dose escalation. We assessed the effect of ADA dose escalation on various outcomes among pts with UC in clinical practice.

Background and Aims Randomised trials have described the benefits of adalimumab [ADA] for ulcerative colitis [UC]; however, few data are available on health-related quality of life [HRQL] and health care costs in clinical practice. Methods InspirADA, a multicentre, prospective study, evaluated the effect of ADA in patients with moderate to severe UC treated according to usual clinical practice. Outcomes assessed were: Simple Clinical Colitis Activity Index [SCCAI] response/remission rates; changes in HRQL; all-cause direct costs; and UC-related direct and indirect costs from baseline to Week 26. Results Data from 463 patients were analysed. At Week 26, 67% (95% confidence interval [CI]: 62%, 71%) of patients achieved response; 48% [95% CI: 44%, 53%] were in remission. For the overall population, significant [all p < 0.001] improvements from baseline to Week 26 were observed for the Short Inflammatory Bowel Disease Questionnaire [SIBDQ] (mean change ± standard deviation [SD]: 17.4 ± 14.5) and the European Quality of Life—5 Dimensions—5 Level [EQ-5D-5L] (index: 0.1 ± 0.2; visual analogue scale [VAS]: 19.5 ± 25.8). Parallel improvements were seen in work productivity [11% absolute decrease in absenteeism; 25% absolute decrease in impairment while working; and 27% absolute decrease in impairment of ability to perform daily activities, all p < 0.001]. Among study completers, cumulative all-cause medical costs and UC-related medical costs were significantly [both p < 0.001] reduced by 59% and 77%, respectively, 6 months after initiation of therapy compared with the preceding 6 months. The safety profile of ADA was consistent with that observed in previous clinical trials. Conclusions ADA therapy in usual clinical practice is effective at improving and maintaining symptomatic control, improving HRQL, and decreasing costs of medical care among patients with UC.

Extraintestinal manifestations (EIMs) are common in patients with ulcerative colitis (UC) and can have a significant impact on patient morbidity and quality of life. We assessed the effect of adalimumab (ADA) therapy on the resolution of EIMs among patients with moderate to severe UC in clinical practice.

Objective.Fatigue and sleep problems are significant in patients with ankylosing spondylitis (AS). This subanalysis of the RHAPSODY study (Review of Safety and Effectiveness with Adalimumab in Patients with Active Ankylosing Spondylitis) was conducted to evaluate the effect of adalimumab on sleep in patients with active AS.Methods.All patients (n = 1250) had active AS and received adalimumab 40 mg every other week during the 12-week open-label treatment period. Sleep was assessed by the Medical Outcomes Study Sleep Scale (MOS-SS) at screening and Weeks 6, 12, and 20 (optional continuation period). Effect sizes were calculated to determine clinical significance. Paired Student t tests compared the change in the MOS-SS domains from Week 12 to baseline. Correlation coefficients were calculated to determine the relationship between change in sleep domains and other Week 12 clinical and patient-reported outcomes (Bath AS Disease Activity Index, C-reactive protein, nocturnal pain, total back pain, Bath AS Functional Index, patient’s global assessment of disease activity, morning stiffness, Short Form-36 Health Survey, and Work Productivity and Activity Impairment questionnaire components).Results.At Week 12, adalimumab significantly improved sleep in each of the MOS-SS domains (p < 0.001). Effect sizes for 3 of the 6 domains (disturbance, −0.69; adequacy, 0.55; somnolence, −0.52) and both sleep problems indices (Index I, −0.68; Index II, −0.77) were moderate, suggesting clinical significance. Change in the MOS-SS Sleep Problem Index II was moderately correlated with change in most clinical and patient-reported outcomes. Sleep improvements were similar in patients with and without radiographically advanced AS.Conclusion.Adalimumab improves overall sleep and sleep quality in patients with active AS.

Despite established genetic and pathophysiologic links between inflammatory bowel disease (IBD) and Parkinson disease (PD), clinical data supporting this association remain scarce. Although systemic inflammation is considered a potential biological mechanism shared between the 2 diseases, the role of reduced systemic inflammation through IBD-directed anti-tumor necrosis factor (anti-TNF) therapy in PD risk is largely unknown.To compare the incidence of PD among individuals with or without IBD and to assess whether PD risk among patients with IBD is altered by anti-TNF therapy.This is a retrospective cohort study analyzing information in the Truven Health MarketScan administrative claims database and the Medicare Supplemental Database between January 1, 2000, and March 31, 2016. Individuals were selected who had at least 2 claims for IBD diagnoses, at least 6 months of follow-up, and no prior diagnosis of PD on or before the IBD index date. Exposure to Anti-TNF therapy was measured from the anti-TNF index date to the last date of anti-TNF coverage or the end of enrollment or PD index date, whichever was earliest. Incidence rates per 1000 person-years were calculated, and crude and adjusted incidence rate ratios were estimated by Poisson regression models and presented with 95% CIs.Incidence of PD among patients with IBD with or without exposure to anti-TNF therapy.In total, 144 018 individuals with IBD were matched on age, sex, and year of index date with 720 090 unaffected controls. Of them, 1796 individuals had at least 2 PD diagnoses and at least 1 filled PD-related prescription. The mean (SD) age of individuals with IBD was 51 (17) years, and 44% were men. The incidence of PD among patients with IBD was 28% higher than that among unaffected matched controls (adjusted incidence rate ratio, 1.28; 95% CI, 1.14-1.44; P .001). A 78% reduction in the incidence rate of PD was detected among patients with IBD who were exposed to anti-TNF therapy compared with those who were not exposed (adjusted incidence rate ratio, 0.22; 95% CI, 0.05-0.88; P = .03).A higher incidence of PD was observed among patients with IBD than among individuals without IBD. Early exposure to antiinflammatory anti-TNF therapy was associated with substantially reduced PD incidence. These findings support a role of systemic inflammation in the pathogenesis of both diseases. Further studies are required to determine whether anti-TNF treatment administered to high-risk individuals may mitigate PD risk.

Introduction Limited real world data are available regarding the effects of adalimumab (ADA) on UK patients with moderate to severe ulcerative colitis (UC). Methods INSPIRADA was a single-arm, multi-country, open-label study that evaluated the effect of ADA on patients with UC treated according to usual clinical practice. Adults with active moderate to severe UC who failed immunosuppressive therapies and experienced rectal bleeding within 7 days of baseline (BL) were enrolled. Prior use of anti-TNF was allowed. Clinical outcomes included Simple Clinical Colitis Activity Index (SCCAI) response (a decrease ≥2 points compared to BL) and remission (SCCAI ≤2). HRQoL (EQ-5D-5L and SIBDQ), treatment satisfaction with medication (TSQM), and work productivity and activity impairment (WPAI) were measured from BL to week 26. Direct medical costs (excluding ADA costs) were estimated using 2014 UK National Health Service reference costs. Indirect costs were based on the WPAI using average weekly earnings from the 2014 UK Annual Salary Survey of Hours and Earnings. Change (defined as 6 mo after start of ADA vs 6 mo before) in resource use and costs were calculated. Data for the intent-to-treat population in UK were analysed. Missing data were imputed using last observation carried forward. Results Data from 90 UK patients (58% male, mean age 39 yrs) were analysed. Mean SCCAI at BL was 8.2. At week 2, 74% achieved SCCAI response and 21% achieved SCCAI remission. At week 8, 73% achieved SCCAI response, 40% in remission and 49% had no blood in stool. At week 26, 66% achieved SCCAI response, 42% in remission and 51% had no blood in stool. Significant improvements, as early as within 2 weeks, in SIBDQ (19.5 points, p Conclusion Real world rates of response, remission and improvements in HRQoL with ADA for UK patients with moderate to severe UC were clinically meaningful. ADA improved work productivity, increased patient satisfaction with therapy and reduced health care associated costs for these patients in the UK. Disclosure of Interest P. Irving Grant/research support from: AbbVie; Falk; Ferring; Genentech/Roche; Hospira; Merck; Pharmacosmos; Shire; Takeda; Tillotts; Topivert; Vifor and Warner Chilcott, Conflict with: Advisor/invited lecturer for: AbbVie; Falk; Ferring; Genentech/Roche; Hospira; Merck; Pharmacosmos; Shire; Takeda; Tillotts; Topivert; Vifor and Warner Chilcott, F. Cummings Conflict with: Advisor/lectures for: Takeda, Abbvie, MSD, Biogen, Napp, Hospira, Janssen, S. Bloom Conflict with: Advisor/lectures for: Takeda, Tillotts, Abbvie, MSD, Pharmacosmos, Vifor, Johnson and Johnson, A. Lazar Shareholder of: AbbVie, Employee of: AbbVie, A. Robinson Shareholder of: AbbVie, Employee of: AbbVie, B. Pappalardo Shareholder of: AbbVie, Employee of: AbbVie, M. Bereswill Shareholder of: AbbVie, Employee of: AbbVie, M. Skup Shareholder of: AbbVie, Employee of: AbbVie, N. Chen Shareholder of: AbbVie, Employee of: AbbVie, T. Finney-Hayward Shareholder of: AbbVie, Employee of: AbbVie, S. Wang Shareholder of: AbbVie, Employee of: AbbVie, R. Thakkar Shareholder of: AbbVie, Employee of: AbbVie, S. Travis Grant/research support from: AbbVie; Asahi; Boehringer Ingelheim; BMS; Cosmo; Elan; Ferring; FPRT Bio; Genentech/Roche; Genzyme; Glenmark; GW Pharmaceuticals; Lilly; Merck; Novartis; Novo Nordisk; Ocera; Pfizer; Shire; Santarus; SigmoidPharma; Synthon; Takeda; Tillotts; Topivert; Trino Therapeutics with Wellcome Trust; UCB Pharma; Vertex; VHsquared; Vifor; Warner Chilcott and Zeria, Conflict with: Advisor or paid instructor for: AbbVie; Asahi; Boehringer Ingelheim; BMS; Cosmo; Elan; Ferring; FPRT Bio; Genentech/Roche; Genzyme; Glenmark; GW Pharmaceuticals; Lilly; Merck; Novartis; Novo Nordisk; Ocera; Pfizer; Shire; Santarus; SigmoidPharma; Synthon; Takeda; Tillotts; Topivert; Trino Therapeutics with Wellcome Trust; UCB Pharma; Vertex; VHsquared; Vifor; Warner Chilcott and Zeria. All advisory boards were suspended Q1 2012–14 while President of ECCO

ObjectivesTumour necrosis factor inhibition plus methotrexate is believed to inhibit radiographic progression independent of inflammation. This analysis assessed whether these protective effects are exerted on bone (joint erosion; JE) and/or cartilage (joint space narrowing; JSN), and what the independent effects of JE/JSN progression are on longer-term patient-reported outcomes.MethodsPREMIER was a 2-year, randomised, controlled trial of adalimumab plus methotrexate (ADA+MTX) versus the monotherapies. The impact of treatment on the relationships between time-averaged disease activity (TA-DAS28(CRP)) and changes in JE/JSN and associations of JE/JSN with the disability index of the health assessment questionnaire (HAQ-DI) at baseline and weeks 52 and 104 were assessed through non-parametric approaches of analysis of variance and quantile regression. JE/JSN association with employment status was evaluated at baseline and weeks 52 and 104 through logistic regression.ResultsIncreasing tertiles of TA-DAS28(CRP) were associated with JE and JSN progression in the monotherapy groups, a phenomenon largely absent in ADA+MTX-treated patients. Although JSN was not associated with HAQ-DI at baseline, it was at 52 and 104 weeks. In contrast, JE was not associated with HAQ-DI at any time point examined. Odds of being employed at baseline, 52 weeks and 104 weeks were significantly associated with lower JSN, but not JE, scores.ConclusionsADA+MTX inhibited both JE and JSN progression independently of disease activity. JSN played a more prominent role in patient-reported outcomes than JE. Preventing the onset or worsening of JSN probably represents a critical aspect of effective disease management of early rheumatoid arthritis patients.

OBJECTIVE: To evaluate open-label adalimumab therapy for clinical effectiveness, fistula healing, patient-reported outcomes and safety in Canadian patients with moderate to severe Crohn’s disease (CD) who were either naive to or previously exposed to antitumour necrosis factor (anti-TNF) therapy.METHODS: Patients with moderate to severe CD (CD activity index [CDAI] score of greater than 220, or Harvey-Bradshaw index [HBI] of 7 or greater) were eligible. Patients received open-label adalimumab as induction (160 mg and 80 mg subcutaneously [sc]) at weeks 0 and 2, respectively and maintenance (40 mg sc every other week) therapy. At or after eight weeks, patients with flare or nonresponse could have their dosage increased to 40 mg sc weekly. Patients were followed for a minimum of six months or until adalimumab was commercially available in Canada.RESULTS: Of the 304 patients enrolled, 160 were infliximab experienced, while 144 were anti-TNF naive. HBI remission (HBI score of 4 or lower) at week 24 was achieved by 53% of anti-TNF-naive and 36% of infliximab-experienced patients (PCONCLUSIONS: Adalimumab therapy induced and sustained steroid-free remission in both infliximab-experienced and anti-TNF-naive patients with moderate to severe CD. Clinically meaningful rates of fistula healing were also observed. Improvements in patient-reported outcomes were sustained throughout the 24-week study period.

Background and aims: Crohn's disease negatively affects patients’ quality of life and ability to work. We investigated the impact of adalimumab on work productivity, daily activities, and quality of life in an open-label trial ( N = 945). The population comprised both infliximab-naive and -exposed patients, including infliximab primary non-responders. Methods: Patients received adalimumab induction therapy (160 mg/80 mg at Weeks 0/2), followed by adalimumab 40 mg every other week for up to 20 weeks (patients with flares/non-response could receive 40 mg weekly at/after Week 12). The Work Productivity and Activity Impairment Questionnaire and Short Inflammatory Bowel Disease Questionnaire were assessed. Indirect cost savings were estimated based on the average work productivity improvements at Week 20. Results: Mean baseline scores indicated severe productivity impairment and poor quality of life. At Week 20, 60% of infliximab-naive and 47% of infliximab primary non-responders achieved clinically important improvements (≥ 9 points) on the Short Inflammatory Bowel Disease Questionnaire, and 51% and 43%, respectively, achieved the minimum clinically important difference (improvement ≥ 7 percentage points) for total work productivity impairment (non-responder imputation). At Week 20, 64% of infliximab-naive and 55% of infliximab primary non-responders achieved clinically important improvements in total activity impairment. Estimated 20-week total indirect productivity-related cost savings were €3070 per infliximab-naive patient and €2059 per infliximab-exposed patient. Conclusions: Adalimumab therapy significantly improved work productivity and disease-specific quality of life for patients with moderate to severe Crohn's disease. Patients who failed prior infliximab therapy and patients naive to infliximab benefited from adalimumab, with potentially greater benefits for infliximab-naive patients ([NCT00409617][1]). * Abbreviations : CARE : Crohn's treatment with adalimumab, patient response to a safety and efficacy study CD : Crohn's disease CRP : C-reactive protein EIMs : extraintestinal manifestations HBI : Harvey Bradshaw Index HRQOL : health-related quality of life MCID : minimum clinically important difference PNR : primary non-responder PRO : patient-reported outcome SIBDQ : Short Inflammatory Bowel Disease Questionnaire TAI : total activity impairment TNF : tumor necrosis factor TWPI : total work productivity impairment WPAI:CD : Work Productivity and Activity Impairment Questionnaire for CD [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00409617&atom=%2Feccojc%2F7%2F1%2F34.atom

Objective The patient acceptable symptom state (PASS) is a single-question outcome tool to assess the level of symptoms at which patients with rheumatic diseases consider themselves well. We evaluated whether ankylosing spondylitis (AS) patient characteristics were associated with attaining the PASS and whether these characteristics influenced PASS thresholds for patient-reported outcome (PRO) tools. Methods The Adalimumab Trial Evaluating Long-term Efficacy and Safety for Ankylosing Spondylitis was a randomized, placebo-controlled study that evaluated the efficacy and safety of adalimumab in treating AS. The PASS and PROs were assessed over 24 weeks. PASS thresholds for PROs were set as either the 25th or 75th percentiles of the PRO response score. Logistic regression analyses were conducted to determine the associations of particular patient characteristics with the PASS and other response outcomes at 12 weeks (ASessment in Ankylosing Spondylitis International Working Group criteria for 20% improvement [ASAS20], ASAS40, ASAS5/6, ASAS partial remission, and Bath Ankylosing Spondylitis Disease Activity Index 50% improvement). Results Age >40 years, disease duration >10 years, female sex, placebo treatment, and English-speaking site were consistently associated with greater PASS thresholds for PROs. Age, male sex, disease duration, and treatment were each independently associated with attainment of the PASS at 12 weeks. Only age and treatment were independently associated with other response outcomes. PASS thresholds also decreased over 24 weeks. Conclusion PASS thresholds for PROs changed over time. These thresholds, as well as the attainment of the PASS, were affected by covariates unrelated to treatment. If confirmed in other studies, these results cast doubt on using the PASS to assess absolute health status in clinical research.

Objective To evaluate the feasibility/acceptability, reliability, external validity, and discriminant capacity of the Patient Acceptable Symptom State (PASS) concept in patients with active ankylosing spondylitis (AS). Methods PASS was assessed by asking patients to respond yes or no to a single question: “Considering all the different ways your disease is affecting you, if you would stay in this state for the next months, do you consider that your current state is satisfactory?” during the 24-week, randomized (2:1 ratio), double-blind, placebo-controlled portion of an adalimumab study of 315 patients. Results PASS reliability was high (κ = 0.86) in patients with stable disease. Significantly more patients who answered yes to PASS than patients who answered no to PASS were responders based on the ASsessment in Ankylosing Spondylitis (ASAS) International Working Group criteria for 20% improvement (75% who answered yes versus 29% who answered no), the ASAS criteria for 40% improvement (61% versus 16%), the ASAS partial remission criteria (37% versus 3%), and ≥50% improvement on the Bath Ankylosing Spondylitis Disease Activity Index (65% versus 19%; P < 0.001 for all comparisons), demonstrating external validity of the PASS concept. More adalimumab-treated than placebo-treated patients achieved PASS at week 12 (42.3% versus 22.4%; P < 0.001), and more adalimumab-treated than placebo-treated patients achieved sustained PASS through week 20 (34.6% versus 12.3%; P < 0.001), indicating excellent discriminant capacity. Conclusion PASS is a feasible, acceptable, reliable, and valid assessment of satisfactory health state in patients with AS.

To compare the effect of adalimumab plus methotrexate (MTX) versus MTX monotherapy on health-related quality of life (HRQOL) and work activities in patients with early rheumatoid arthritis (RA).Patients in this PREMIER study subanalysis (n = 525) were randomized to adalimumab 40 mg every other week plus MTX or MTX monotherapy. Medical Outcome Study Short-Form 36 Health Survey (SF-36) scores of RA patients were compared with US population norms at Weeks 12, 52, and 104.Physical Component Summary (PCS) scores at Week 12 for both groups improved from baseline and were significantly lower than US population scores (43.5 combination, 39.4 MTX, 49.4 US norm; p0.001). At Week 52, PCS score for adalimumab plus MTX was similar to that of the US population (47.5 vs 48.3; p = 0.25), while the PCS score for MTX was not similar to that of the US population (44.2 vs 48.3; p0.001). Criterion- and content-based interpretations for between-treatment differences in PCS scores suggest that those receiving combination therapy had fewer employment difficulties than those receiving MTX.After 2 years, HRQOL for patients with early RA treated with adalimumab plus MTX improved to US norms. Combination therapy had reduced the influence of RA on work activity.

Background ASAS40 response has been used as a primary endpoint in clinical trials of patients (pts) with axial spondyloarthritis (axSpA), and ASDAS inactive disease is recommended as a treatment target. However, the relationships between these clinical measures and patient-reported outcomes (PROs) are not well understood. Objectives To assess the impact of achieving ASAS40 response or ASDAS inactive disease state on PROs among pts with non-radiographic axSpA (nr-axSpA). Methods Data were drawn from ABILITY-1, a Phase 3 trial of adalimumab (ADA) vs. placebo (PBO) in pts with nr-axSpA (meeting ASAS axial SpA criteria but not modified New York criteria for AS) 1 . Pts (N=185) were randomized to ADA or PBO for 12 weeks of double-blind treatment. Physical function was assessed with the disability index of the Health Assessment Questionnaire for the Spondyloarthropathies (HAQ-S). HRQOL was assessed with the Short Form 36 Health Survey (SF-36) Physical Component Summary (PCS) score. Work productivity was assessed with the Work Productivity and Activity Impairment (WPAI) Questionnaire. For this analysis, pts were grouped by clinical responses i.e., ASAS40 response and disease activity state (inactive [ASDAS 3.5]) at week 12 and further stratified by treatment arm (ADA vs. PBO). Changes in PROs from baseline to Week 12 were compared between groups using ANCOVA with adjustment for baseline scores. Results Mean baseline HAQ-S and SF-36 PCS scores were 1.02±0.56 and 33.5±8.0, respectively. Mean baseline WPAI domain scores were 57.1±24.7 (activity impairment), 9.8±20.9 (absenteeism), 43.3±25.7 (presenteeism), and 47.5±27.9 (work impairment). At Week 12, clinical improvement was greater in pts on ADA vs. PBO; 47 of 179 pts with non-missing data (38% of ADA vs. 15% of PBO pts, p Conclusions Among pts in ABILITY-1, both ASAS40 response and ASDAS inactive disease state were associated with meaningful improvements in PROs. References Sieper J, et al. Ann Rheum Dis. 2013;72(6):815–22. Revicki D, et al. Arthritis Rheum. 2012;64(10 Suppl):S1-1216. van der Heijde DM, et al. Arthritis Res Ther. 2009;11(4):R124. Sandborn WJ, et al. Gut. 2007; 56(Suppl 3):A159, Abstract MON-G-355. Acknowledgements Eric Bertelsen, PhD, of Arbor Communications provided medical writing and editing services in the development of this abstract. Financial support for these services was provided by AbbVie. Disclosure of Interest D. van der Heijde Consultant for: AbbVie, Amgen, Aventis, Bristol-Myers Squibb, Centocor, Pfizer, Roche, Schering-Plough, UCB, Wyeth, A. Joshi Shareholder of: AbbVie, Employee of: AbbVie, M. Mittal Shareholder of: AbbVie, Employee of: AbbVie, A. Pangan Shareholder of: AbbVie, Employee of: AbbVie, N. Chen Shareholder of: AbbVie, Employee of: AbbVie, K. Betts Employee of: Analysis Group, which received payment from AbbVie to assist with the research, C. Qi Employee of: Analysis Group, which received payment from AbbVie to assist with the research, Y. Bao Shareholder of: AbbVie, Employee of: AbbVie DOI 10.1136/annrheumdis-2014-eular.2376

Paul Emery, Josef Smolen, Arijit Ganguli, Sebastian Meerwein, Yanjun Bao, Hartmut Kupper, Naijun Chen, P. Mahinda Karunaratne and Arthur Kavanaugh Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds and NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospital, Leeds, UK, Division of Rheumatology, Medical University of Vienna and Hietzing Hospital, Vienna, Austria, Health Economics & Outcomes Research, AbbVie Inc., North Chicago, IL, USA, Clinical Development, AbbVie Deutschland GmbH and Co. KG, Ludwigshafen, Germany, Division of Statistics, AbbVie Inc., North Chicago, IL, Division of Rheumatology, University of California San Diego, La Jolla, CA, USA

Background & Aims Patients with moderate to severe ileocolonic Crohn's disease (CD) who received adalimumab induction and maintenance therapy had greater rates of mucosal healing than patients who received placebo after adalimumab induction therapy in a 52-week trial (EXTend the Safety and Efficacy of Adalimumab Through ENDoscopic Healing). We investigated whether this treatment also induced deep remission—a composite clinical and endoscopic end point. Methods Rates of deep remission, defined as the absence of mucosal ulceration and CD Activity Index scores less than 150, were compared between patients given continuous adalimumab and those given only induction therapy followed by placebo. We assessed the relationships between deep remission and other outcomes among patients who received adalimumab. The outcomes of patients with deep remission were compared with those of patients with only the absence of mucosal ulceration or only clinical remission. Results Rates of deep remission were 16% in patients given adalimumab vs 10% in those given placebo (P = .34) at week 12, and 19% vs 0% (P Conclusions In an exploratory study of patients with moderate to severe ileocolonic CD who received adalimumab induction and maintenance therapy, patients achieving deep remission appeared to have better 1-year outcomes than those not achieving deep remission. These findings should be validated in large, prospective trials. ClinicalTrials.gov number: NCT00348283.

Adalimumab is effective for induction and maintenance of remission in patients with moderate to severe ulcerative colitis (UC). We assessed whether adalimumab, in addition to standard UC therapy, reduced the risk for hospitalization (from all causes, from complications of UC, or from complications of UC or the drugs used to treat it) and colectomy in patients with moderate to severe UC compared with placebo.Data were combined from patients that received induction therapy (a 160-mg dose followed by an 80-mg dose of adalimumab) or placebo in 2 trials (ULTRA 1 and ULTRA 2; n = 963). The risks of hospitalization and colectomy were compared between groups using unadjusted rates during the 8-week induction period, and patient-year-adjusted rates during 52 weeks. Statistical differences between groups were determined using the χ(2) method and Z score normal approximations. Numbers of hospitalizations were compared using Poisson regression with time offset.Significant reductions in risk of all-cause, UC-related, and UC- or drug-related hospitalizations (by 40%, 50%, and 47%, respectively; P.05 for all comparisons) were observed within the first 8 weeks of adalimumab therapy compared with placebo. Significantly lower incidence rates for all-cause (0.18 vs 0.26; P = .03), UC-related (0.12 vs 0.22; P = .002), and UC- or drug-related (0.14 vs 0.24; P = .005) hospitalizations were observed during 52 weeks of adalimumab therapy compared with placebo. Rates of colectomy did not differ significantly between patients given adalimumab vs placebo.In patients with moderate to severe UC, the addition of adalimumab to standard of care treatment reduced the number of hospitalizations for any cause, as well as for UC-related and UC- or drug-related complications, compared with placebo. ClinicalTrials.gov numbers, NCT00385736 and NCT00408629.

Introduction We explored the relationship between early deep remission and rates of dosage adjustment for patients (pts) with Crohn9s disease (CD). Methods EXTEND studied the effects of adalimumab (ADA) on mucosal healing in pts with moderate to severe ileocolonic CD (CDAI 220–450). Pts received open-label (OL) ADA 160-/80-mg induction therapy at weeks 0/2 and were randomised at week 4 to maintenance therapy with ADA 40 mg every other week (eow) or placebo through week 52. From week 8, pts with flares or non-response could receive OL ADA 40 mg eow. The maintenance regimen could be adjusted to weekly OL ADA for continued flares/non-response. Endoscopic assessments of mucosal disease activity were performed at baseline, week 12 (or unscheduled visits weeks 8–12 prior to switch to OL), time of switch to OL ADA (if after week 12) and week 52 (or early termination). Early deep remission was defined as mucosal healing (visually determined) plus clinical remission (CDAI Results 64 pts were randomised to ADA maintenance therapy at week 4. ADA-treated pts who achieved deep remission by week 12 had significantly lower rates of dosage adjustment compared with pts not achieving early deep remission (table 1). No pts achieving early deep remission moved to weekly therapy. Conclusion Deep remission, defined as complete mucosal healing plus clinical remission, may be an important treatment goal in CD. Pts in EXTEND who achieved deep remission by week 12 were less likely than those not achieving deep remission to move to OL eow dosing and subsequently receive weekly therapy.