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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

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.

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.

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.

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.

Introduction: Adalimumab (ADA) was efficacious in the induction and maintenance of remission and in improving quality of life (QOL) for patients (pts) with Crohn's disease (CD) in CHARM.1,2 The current analysis assessed the long-term effects of ADA on QOL for pts in ADHERE, an open-label extension of CHARM. Methods: In CHARM, pts were randomized to placebo, 40-mg ADA every other week (eow), or 40-mg ADA weekly. Pts with flare/nonresponse could receive open-label (OL) ADA at/after Week 12. At the end of CHARM (56 weeks), pts could enter ADHERE; pts on blinded therapy received ADA eow and those on OL ADA maintained their therapy. In CHARM and ADHERE, pts could change from eow to weekly dosages for flares/nonresponse. Pts were followed for 3 years (yrs) from CHARM baseline. Efficacy and QOL were assessed by using the Inflammatory Bowel Disease Questionnaire (IBDQ) and Short Form-36 (SF-36) Mental Component Summary (MCS) and Physical Component Summary (PCS). Results: This analysis included 328 ADA-treated pts who entered ADHERE. At both 2 yrs and 3 yrs from CHARM baseline, >50% of ADAtreated pts achieved IBDQ≥170 (Table). Statistically significant improvements in mean total IBDQ and SF-36 PCS and MCS scores were also observed at both time points. Conclusions: Clinically important improvements in QOL achieved with ADA in the CHARM trial were sustained through 3 yrs of ADA maintenance therapy. References 1. Colombel J-F, et al. Gastroenterology. 2007;132:52-65. 2. Loftus EV, et al. Am J Gastroenterol. 2007;102(Suppl 2):S456.

BACKGROUND: Natalizumab (NAT), a monoclonal antibody to α4-integrin, was recently approved by the FDA for use in the treatment of moderate to severe Crohn's disease (CD). AIM: To prospectively report the clinical outcomes and safety in patients (pts) treated with NAT at a tertiary care IBD center. METHODS: Eighteen pts with moderate to severe CD treated in clinical practice with intravenous NAT every 4 weeks were enrolled in a registry. Patients were assessed for clinical response to NAT (categorized as complete response [CR], partial response [PR], or no response [NR]), steroid reduction, and adverse events (AE). RESULTS: The median age of this group was 43.5 years (range 20-63) with median disease duration of 13 years (range 3-43). All patients had failed prior anti-TNF therapy (median of 2 agents). Twelve pts (67%) had ileocolonic CD at diagnosis and 5 (28%) had undergone colectomy prior to NAT. The median follow-up was 88 days (range 3-219). Two pts had screening brain MRI or CT prior to NAT. Pts received one to eight infusions of NAT for a total of 77 infusions. In total, 2 pts (11%) had CR, 13 (72%) had PR and 3 (17%) had NR. Two pts achieved complete mucosal healing as documented by radiography. There were 6 pts on corticosteroids; 4 prior to NAT and 2 initiated during treatment. One pt successfully completed prednisone taper and 2 pts are currently tapering (mean dose change 7.5 mg). Sixteen pts (89%) had a total of 55 AE. Clinically significant AE included 1 ileocolonic resection due to active CD with high-grade dysplasia found in surgical specimen, 1 abdominal wall abscess, 1 Epstein Barr virus febrile infection, 3 infusion reactions characterized by rash, pruritus or throat irritation and 4 hospitalizations secondary to volume depletion (2), abscess drainage (1) and fever work-up (1). Eight pts (44%) complained of headache following infusions and 1 of loss of balance and tinnitus. Two patients with neurologic symptoms underwent brain CT or MRI evaluations, which were negative. Minor infectious AE included 4 upper respiratory tract infections and 1 each of conjunctivitis, sinus infection, cystitis and otitis. Only 1 pt discontinued NAT due to an infusion reaction and acute infectious colitis. CONCLUSIONS: In this initial clinical practice experience, NAT was a clinically beneficial and well-tolerated option for patients with CD who had lost their response to, or who could not tolerate, anti-TNF agents.

Introduction: Adalimumab (ADA) was efficacious in the induction and maintenance of remission and in improving quality of life (QOL) for patients (pts) with Crohn's disease (CD) in CHARM.1,2 The current analysis assessed the long-term effects of ADA on QOL for pts in ADHERE, an open-label extension of CHARM. Methods: In CHARM, pts were randomized to placebo, 40-mg ADA every other week (eow), or 40-mg ADA weekly. Pts with flare/nonresponse could receive open-label (OL) ADA at/after Week 12. At the end of CHARM (56 weeks), pts could enter ADHERE; pts on blinded therapy received ADA eow and those on OL ADA maintained their therapy. In CHARM and ADHERE, pts could change from eow to weekly dosages for flares/nonresponse. Pts were followed for 3 years (yrs) from CHARM baseline. Efficacy and QOL were assessed by using the Inflammatory Bowel Disease Questionnaire (IBDQ) and Short Form-36 (SF-36) Mental Component Summary (MCS) and Physical Component Summary (PCS). Results: This analysis included 328 ADA-treated pts who entered ADHERE. At both 2 yrs and 3 yrs from CHARM baseline, >50% of ADAtreated pts achieved IBDQ≥170 (Table). Statistically significant improvements in mean total IBDQ and SF-36 PCS and MCS scores were also observed at both time points. Conclusions: Clinically important improvements in QOL achieved with ADA in the CHARM trial were sustained through 3 yrs of ADA maintenance therapy. References 1. Colombel J-F, et al. Gastroenterology. 2007;132:52-65. 2. Loftus EV, et al. Am J Gastroenterol. 2007;102(Suppl 2):S456.

have pseudopolyposis in 20/146 pts (13%) (c2 test=1.02; p value NS). In the group of UC pts there are 31with left-sided disease and 61 with pancolitis. In the left sided group indidence of pseudopolyposis is 29% (9/29), and in pancolitis 11% (10/61) (c2 test 0.75, p value NS). Conclusion: There is no difference in prevalence of pseudopolyposis in patients with ulcerative colitis and Crohn colitis in our cohort, also no difference in incidence regarding the initial extension of the disease in UC. We can conclude that phenotype (UC:CC) isn’t relevant for the development of colonic pseudopolyposis.

Introduction:Work Productivity and Activity Impairment (WPAI) questionnaire is a validated, self-administered tool that assesses the impact of disease on productivity. The Short Inflammatory Bowel Disease Questionnaire (SIBDQ) is a simple, validated, 10-item instrument that assesses health-related quality of life (HRQOL) in patients with inflammatory bowel disease. In the Crohn’s Patients Treated With Adalimumab: Results of a Safety and Efficacy Study (CARE), the efficacy and safety of adalimumab in a large population of patients whose treatment approximated usual clinical practice were evaluated. In this analysis, we investigated the impact of adalimumab treatment on work productivity and HRQOL in CARE. Methods: A total of 945 patients with Harvey Bradshaw Index score >7 enrolled in this multicenter, open-label, European, Phase IIIb trial. The study population included patients naive to biotherapy and patients who had failed infliximab therapy (primary nonresponders [PNR] to infliximab, lost response to infliximab, intolerant of infliximab, and other infliximab failures). Patients received induction therapy of 160-mg/80-mg adalimumab at Weeks 0/2, followed by adalimumab 40mg every-other-week maintenance therapy through at least Week 20 (patients with flares/nonresponse could receive 40mg weekly at/after Week 12). In this analysis, patients’ work productivity, as measured by WPAI, and HRQOL, as measured by SIBDQ, were analyzed. The WPAI tool, as adapted for CD, measures the percentage of overall impairment in work productivity (including absenteeism and presenteeism) and daily activity due to CD (0%=no impairment, 100%=total loss of work productivity/activity). An absolute change of 7% in WPAI score is the minimum clinically important difference (MCID). SIBDQ total scores range from 10 70, with greater scores indicating better HRQOL. A 9-point change in SIBDQ is correlated with a 100-point change in CDAI score. Both measures were assessed at baseline and Weeks 4, 8, 12, and 20, and changes from baseline were analyzed using paired Student t-tests. Results: Mean age of patients was 35.3 years, and 60% were female. Mean baseline total daily activity impairment (TAI) was 57% (n = 907). For employed patients, total work productivity impairment score (TWPI) was 51% (n = 442) at baseline, indicating severe impairment. Baseline quality of life of patients was substantially impaired (SIBDQ mean = 37±10). Mean changes in WPAI components and SIBDQ are summarized by reason for infliximab failure (table). Overall, at Week 20, 57% (518/910), 62% (559/907), and 47% (208/442) of patients achieved improvement of SIBDQ of 9 points (correlated with 100-point change in CDAI), TAI of at least 7 points (MCID), and TWPI of 7 points (MCID) (NRI). Conclusions: Adalimumab therapy significantly improved work productivity and quality of life for patients with moderately to severely active CD, including those naive to anti-TNF therapy and those who had failed infliximab therapy. These improvements were observed as early as Week 4 and maintained throughout the study. Mean absolute change in SIBDQ and two WPAI subscores with adalimumab therapy at Weeks 4 and 20 in CARE by prior use of infliximab (observed)

A C). Four of them (57%) had fistula associated CRC. They suffered from CD for a median of 13 years (range 12 33). Seven patients with CRC were matched 1:3 to randomly selected Crohn’s patients based on age (9 male, 12 female). The medical records of these patients were evaluated with respect to duration and pattern of intestinal involvement of CD, fistula history, intestinal surgery, perianal surgery, prior immunosuppressive and 5-ASA derivative intake. Three patients of the matched group had involvement of the terminal ileum, 13 of ileocolon, 1 of upper GI and 4 of ileocolon and upper GI tract, with a disease duration of a median of 26 years (range 5 62). From these 21 patients 11 suffered from perianal fistula (52%). Results: Colorectal cancer was significantly (p = 0.048) associated with longstanding anorectal fistula (median = 11 years, range 0 28) in the CRC group compared to the matched Crohn’s patients [median = 1 year (range 0 6)]. The formation of cancer in a fistula showed a significant (p = 0.08) correlation with duration of the perianal disease. Earlier colonic surgery seemed to protect from later malignancy (p = 0.036; 16 matched controls had colonic surgery versus 2 patients in the CRCgroup). No significant symptoms preceded rectal carcinoma, except for new blood drainage from fistula in 2 patients. Two patients underwent ileocolonoscopy within 1 year before the diagnosis of malignancy without hint of dysplasia or carcinoma and 2 patients underwent MRI of the pelvic region within 4 months before surgery without recognizing malignant changes. There were no significant differences in 5-ASA, azathioprine intake or infliximab therapy, perianal surgery, extension and duration of the Crohn’s disease in both groups. The one year survival rate was 84% in patients with CRC. Conclusion: Colorectal carcinoma is generally rare in patients with Crohn’s disease, but is frequently associated with the presence of longstanding (>10 years of duration) anorectal fistula. It occurred with minimal change of symptoms and was not visible in previous MRI.

s of the 4th Congress of ECCO the European Crohn’s and Colitis Organisation S13 Of selected patients clinical data including age, gender, type of IBD, date of diagnosis of IBD and CRC, follow-up of IBD and CRC and extend of disease were collected from patient charts. Statistical analysis was performed using descriptive statistics, Kaplan Meier & log-rank tests and Cox-regression analysis. Results: In total, 78 of all 93 Dutch non-academic centers participated. We assessed 430 patient-charts and pathology reports. In 197 patients 65 years old, diagnosis of IBDrelated CRC was confirmed: 125 had ulcerative colitis (UC), 69 Crohn’s disease (CD) and 3 Indeterminate Colitis. Sixtyfour percent were males (126/197), 20 patients had PSC (10%), mean age at diagnosis of IBD was 35 years (±15) and of CRC 50 years (±10.6). Eighty-four patients (44%) had T3 tumors and 31 (16%) already had metastases at time of diagnosis. Mean time from diagnosis of IBD to diagnosis of CRC was 15.3 years (±11.7). Type of IBD, gender, concomitant PSC and/or pseudopolyps, and gravityand extension of inflammation were not significantly associated with time to diagnosis of CRC. Although the latter was not significant (p = 0.063), contrary to surveillance guidelines, there was a trend for patients with extensive UC to develop CRC at later stage (mean 16.7 years) than patients with left-sided colitis (mean 11 years). Diagnosis of IBD at older age was associated with earlier development of CRC (OR 1.09; 95%CI 1.07 1.10). Forty-eight percent of tumors were located in rectum or sigmoid and 73% occurred in previous inflamed areas. Location of inflammation was not predictive for tumor-location, but UC patients developed more left-sided tumors than CD patients (p = 0.022). In 58 hospitals the size of the IBD population could be assessed: 26,855 patients in total, of whom only 163 developed a CRC during 15 years follow-up. Conclusion: The risk of IBD-associated CRC is limited in a regular, secondary IBD population. Current surveillance strategies need to be adjusted, including equalisation of strategies for left-sided and pancolitis. A nested case-control is being performed, of which the results are expected early in 2009. P006 Sustainability of adalimumab in improving the quality of life of patients with fistulizing Crohn’s disease: 3-year data from CHARM D.A. Schwartz1 *, J.F. Colombel2, R. Panaccione3, B. Feagan4, M.A. Kamm5, N. Chen6, J. Chao6, P. Mulani6. 1Vanderbilt University Medical Center, Nashville, TN, USA, 2Hopital Claude Huriez, Centre Hospitalier Universitaire de Lille, Lille, France, 3University of Calgary, Calgary, AB, Canada, 4Robarts Research Institute, London, ON, Canada, 5University of Melbourne, Melbourne, Australia, 6Abbott, Abbott Park, IL, USA Introduction: Fistulas occur in 17% to 43% of patients with Crohn’s disease (CD) [1]. A previous analysis demonstrated that adalimumab improved qualify of life (QOL) for patients with fistulizing CD [2]. The objective of this analysis was to assess the long-term efficacy of adalimumab on QOL in patients with fistulizing disease through 3 years after enrollment in the CHARM trial. Methods: Patients in CHARM were randomized to placebo, adalimumab 40mg every other week (eow), or adalimumab 40mg weekly. At or after Week 12, patients with flare (increase in CD Activity Index [CDAI] 70 points compared with Week 4 and CDAI > 220) or nonresponse (did not attain 70-point decrease in CDAI compared with baseline) were switched to open-label adalimumab 40mg eow. At the end of CHARM (56 weeks), patients could enroll in an open-label extension (ADHERE), in which patients who completed CHARM on blinded therapy received open-label adalimumab eow and those already receiving open-label treatment maintained their therapy. In ADHERE, patients could change from eow to weekly treatment for flares or nonresponse. This analysis included patients who had fistulas at CHARM baseline, were randomized to adalimumab (eow or weekly) in CHARM, and enrolled in the open-label extension. The two adalimumab arms were combined for analysis. QOL measures evaluated included the Inflammatory Bowel Disease Questionnaire (IBDQ) and Short Form 36 (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS) scores over time. Data were compared with baseline using the paired Student t-test. The percentages of patients with IBDQ 170 (which correlates with clinical remission) and who achieved an IBDQ change 16 (IBDQ minimum clinically important difference [MCID]) from baseline were also calculated. Last-observation-carried-forward (LOCF) analyses were used. Results: The table presents mean QOL measures for all fistulizing patients (n = 48) for the combined adalimumab groups. Statistically significant improvements from baseline were observed at Weeks 60 and 108 in the open-labelextension, representing approximately 2 and 3 years, respectively, from CHARM baseline. IBDQ remission was achieved in 60% of patients at 2 years from CHARM baseline and in 52% at 3 years from CHARM baseline. MCID for IBDQ was achieved in 81% of patients at 2 years from CHARM baseline and 79% of patients at 3 years from CHARM baseline. Long-term efficacy of adalimumab (EOW and weekly combined) on remission and QOL measures in patients with fistulas: LOCF analysis