Year Of Biologic Therapy Research Articles

Biologic Therapy and Cardiometabolic Risk in Psoriasis: A Retrospective Review.

Psoriasis is a systemic inflammatory disease with increased cardiometabolic risk including dyslipidaemia and diabetes. Biologic therapy effectively treats the cutaneous inflammatory burden of psoriasis and evolving evidence suggests potential to reduce systemic inflammatory sequalae that can elevate cardiovascular risk. This study aimed to assess the change in cardiometabolic risk markers in a cohort of patients with psoriasis treated with 1year of continuous biologic treatment. A retrospective review was conducted of patients receiving biologic therapy for chronic plaque psoriasis in a single dermatology centre at a major tertiary hospital in Sydney, Australia. The effect of biologic therapy on psoriasis was assessed using the psoriasis area severity index (PASI). Cardiometabolic risk markers assessed included lipid profile (total cholesterol [TC], low-density lipoprotein [LDL] cholesterol, high-density lipoprotein [HDL] cholesterol and triglycerides [TG]) and haemoglobin A1c (HbA1c). Measurements at baseline and 1year were compared using paired ttests for analysis of the parameters which approximated normal distribution (TC, LDL, HDL) and Wilcoxon signed-rank test for analysis of those which did not (TG, HbA1c, PASI). Two-tailed Pvalues < 0.05 were considered significant. A total of 200 patients were reviewed, of which 39had complete data sets. The participants' ages ranged from 21 to 85years (mean 51, SD 16.9). Of the 39 participants, 31 (79.5%) were male, 8 (20.5%) were female; 26 (67%) were biologic experienced (BE) and 13 (33%) were biologic naïve (BN). The mean PASI at baseline (for BN + BE) was 13.4 (SD 9.8). The biologic agents used, according to frequency, included risankizumab, with 14 participants (35.9%), secukinumab by 7 (17.9%), ustekinumab by 6 (15.4%), ixekizumab by 6 (15.4%), guselkumab by 3 (7.7%), infliximab by 2 (5.1%), and adalimumab by 1 (2.6%). After 12months, significant skin improvement was seen [PASI reduced from 13.43 (SD 9.8) to 1.1 (SD 2.1), p < 0.001]. There was no significant change in lipid profile, including TC (mean difference -0.1mmol/L, p = 0.532), LDL-C (mean difference = -0.1mmol/L, p = 0.476), HDL (mean difference = -0.1mmol/L, p = 0.125), triglycerides (mean difference = 0.0mmol/l, p = 0.748) or HbA1c (mean difference 0.38%, p = 0.468). Markers of cardiometabolic risk (lipid profile and HbA1c) did not significantly improve after 1year of biologic therapy despite significant reduction in psoriasis skin severity. Further research in larger cohorts is needed to elucidate the benefits, if any, of biologic therapy on cardiometabolic parameters in individuals with psoriasis, in order to optimise care for this vulnerable cohort.

Impact of Biologic Therapy on Key Cardiovascular Risk Parameters in a Psoriatic Cohort-a Retrospective Review.

Psoriasis is a risk factor for cardiovascular disease. Biologic agents have revolutionised psoriatic skin control. This study aims to assess the change in cardiovascular risk factors in a cohort of patients treated with 1 year of continuous biologic treatment. A retrospective medical record review was conducted of consecutive patients receiving biologic therapy for chronic plaque psoriasis in a single dermatology centre at a major tertiary hospital in Australia. The effect of biologic therapy on psoriasis was assessed using a psoriasis area severity index (PASI). Cardiovascular risk factors included systolic blood pressure (SBP), diastolic BP (DBP), heart rate (HR) and body mass index (BMI). Measurements at baseline and 1-year follow-up were compared using paired t-tests. A total of 106 patients were reviewed with a median age of 44 years, and 63% of the patients were male. At baseline, mean BMI was 30 (SD 7), mean SBP was 129 (SD 17), mean DBP was 81 (SD 9) and mean HR was 82 (SD 14). Over 12months, the PASI was reduced from 17.4 (SD 8.5) to 1.4 (SD 1.7, p < 0.001) indicating skin improvement. There was no significant difference from baseline in SBP (difference 2.3mmHg, 95% CI - 1.4-5.9), DBP (0.6mmHg, 95% CI - 1.2-2.5), BMI (difference - 0.1kg/m2, 95% CI - 0.9-0.7) or HR (difference 1.3, 95% CI - 3.9-6.4). In patients with psoriasis, markers of cardiovascular disease risk did not improve after 1year of biologic therapy despite significant improvements in psoriasis skin severity.

Dupilumab's impact on nasal citology: Real life experience after 1 year of treatment

BackgroundBiologic agents are considered a new revolutionized therapy for severe and recurrent forms of CRSwNP which disease burden is not sufficiently controlled by conservative and/or surgical treatments. Recent Research has focused on evaluating their real-life efficacy in CRSwNP, as only limited reports on real-life data are available. However, in most studies, the response to treatment is evaluated in terms of improvement in Nasal Polyp Score (NPS) or in Sino-Nasal Outcome test (SNOT-22) scores. However, both criteria do not consider nasal immunophlogosis, which can be easily assessed by nasal cytology.The aim of our study was to evaluate changings in the nasal inflammatory infiltrate of CRSwNP patients treated with Dupilumab for 12 months. Methods27 patients suffering from severe CRSwNP treated with Dupilumab were recruited. Nasal cytology findings, NPS, SNOT-22, ACT scores and blood eosinophil count at T0 (before treatment) and at T1 (after 1 year of treatment) were compared. ResultsAfter 1 year of biological therapy with Dupilumab, NPS, SNOT-22 and, among the 17 asthmatic patients, ACT scores improved significantly. At T1, a statistically significant percentage of patients showed negative citology. Moreover, a significant reduction in the mast cell-eosinophilic pattern and an increase of neutrophils and bacteria was reported. ConclusionsThe response to treatment can be considered both in the case of negative nasal cytology and in the case of the appearance of neutrophils and bacteria. In this context, eosinophils, the specific target of biological therapies, play a crucial role in regulating tissue homeostasis and, consequently, the nasal immunophlogosis.

A76 COMBINING TOFACITINIB AND USTEKINUMAB FOR REFRACTORY ULCERATIVE COLITIS: A CASE REPORT

Abstract Background The paradigm for Inflammatory Bowel Disease (IBD) management has shifted towards prioritizing remission of inflammation over symptom control, emphasizing sustained, corticosteroid-free remission at the clinical, endoscopic, and histologic levels. The shift is due to the recognition that uncontrolled inflammation often causes morbidity; after one year of biological therapy, 40% of patients still experience persistent disease activity. Several approaches have been proposed to address this challenge, including drug level monitoring, dosage titration, antibody screening, and, as a last resort, surgical intervention. Emerging limited studies suggest the potential efficacy of combining two biological agents or a biological agent with small molecules in IBD, contrasting the efficacy and safety concerns encountered with their use in rheumatological diseases. Aims To describe a case of successful combination therapy with Tofacitinib and Ustekinumab in refractory Ulcerative Colitis with a review of the current literature. Methods This case describes a 35-year-old male patient with severe Ulcerative Colitis refractory to 5-ASA, Azathioprine, Infliximab with Methotrexate, Vedolizumab, Ustekinumab and Tofacitinib. His disease persisted with primary treatment failures requiring hospital admissions and rescuing with parenteral steroids. He was switched back to Ustekinumab with minimal symptom improvement but required repeated steroid courses to achieve control. After deliberations, Tofacitinib was added. This combination achieved remission of his symptoms and inflammatory markers, mainly guided by fecal calprotectin (from 3728 µg/g to 46 µg/g), as well as endoscopic and histologic remission. He is being weaned off the oral budesonide he had been on to augment his response. Results After 4 years of combination therapy, he remains in remission with no adverse events or infections. Reassuringly, Janus Kinase inhibitors (i.e., Tofacitinib) have a short half-life, allowing prompt discontinuation if indicated, especially in the event of infection. Furthermore, biologics such as Vedolizumab, Ustekinumab, and Risankizumab offer minimal systemic immunosuppression and do not appear to raise the risk of infection. Apart from safety concerns and limited data on the use of combination therapy, significant economic implications exist. However, the attainability of cheaper generic forms of small molecules (e.g., Tofacitinib roughly costs a quarter of the brand price in Ontario, Canada) adds another advantage to their combination use. Conclusions Combination therapy with biologics and small molecules is a potential consideration for treating severe or refractory Ulcerative Colitis or IBD. To bridge the knowledge gap regarding combination therapies in IBD, further studies are needed on efficacy, safety, long-term effects, and economic impact. Funding Agencies None

The Outcome of Ulcerative Colitis Patients after One Year of Biological Therapy

Background Inflammatory bowel disease (IBD) comprises two types, namely, the ulcerative colitis (UC) and Crohn’s disease (CD). They are a spectrum of chronic idiopathic autoimmune inflammatory disorders with remission and relapses, primarily affecting the gastrointestinal system, UC is characterized by confluent mucosal inflammation and erosions starting from the anal verge and extending to a variable extent, where Patients often complain of diarrhea associated with rectal bleeding, abdominal tenderness, and weight loss A number of biological agents have been approved by the U.S Food and Drug Administration (FDA) for te treatment of UC. Objectives The aim beyond this study is to assess the effect of biological therapy after one year on ulcerative colitis patients regarding clinical manifestations, hospitalization, number of severe attacks, laboratory investigations, colonoscopy and histopathology. Patients and Methods The studied patients were selected from patients presented to IBD study group clinic.tropical medicine department in Ain Shams University hospitals. total number of cases during the study period was 28 cases fulfilling the inclusion criteria. Results The mean age of the patients was 30.14 ± 7.65. The majority of the cases were sightly more common in females. The duration of illness ranged from 1-10 years with median 3 years (2 - 5.5). the majority of the patients had pan colitis (75%). there were 19 biologic-naive patients (67.9 %) and 9 biologic-experienced patients (32.1%). In our study, 16 patients (57.1%) received adalimumab, 11 patients (39.3%) received infliximab and only one patient received ustekinumab. The majority of cases (71.4%) were taking azathioprine as a combination therapy with biologics. the majority of the patients (75%) achieved clinical response at 1-year follow-up.While clinical remission achievied in only 46.4% Conclusion Biological treatments are very successful in the therapy of IBD. However, these treatments are still expensive and new patients with IBD must begin first with the traditional treatments without knowing if they will work for them.

Abstract 9816: Cholesterol Efflux Capacity Mediates The Relationship Between Neutrophils And Coronary Burden In Psoriasis

Introduction: Psoriasis is a chronic inflammatory disease associated with increased levels of activated neutrophils, lower cholesterol efflux capacity (CEC), and subclinical atherosclerosis. High-density lipoprotein cholesterol efflux is the primary method of cholesterol removal from peripheral tissues and is linked to innate immunity and cardiovascular disease. Preclinical models suggest a strong relationship between CEC, neutrophil frequency and activation, and atherosclerosis, yet this relationship is understudied in clinical models. Hypothesis: (1) Psoriasis patients with high neutrophils have lower CEC and high non-calcified coronary burden (NCB); (2) CEC mediates the relationship between neutrophils and NCB. Methods: Coronary computed tomography angiography was used to quantitate NCB in one-hundred seventy-nine untreated psoriasis patients. Circulating neutrophils were measured via flow cytometry, and mean fluorescence intensity of CD62L and CD11b was determined. CEC was quantified using a cell-based ex-vivo assay measuring the ability of apolipoprotein B depleted plasma to mobilize cholesterol from lipid-loaded macrophages. Results: Patients with high neutrophils had decreased CEC (0.93 (0.15) vs 1.00 (0.17); P =0.03) and higher NCB (1.24 (0.55) vs 1.10 (0.50); P =0.003). The relationship between neutrophils and NCB was mediated by CEC beyond adjustment for Framingham risk score, smoking status, and statin treatment (20%, P =&lt;0.001) ( Figure 1 ). CEC associated with neutrophil activation markers, CD11b and CD62L (β: -0.23 P =0.04, β:0.21, P =0.04). Finally, one year of biologic therapy improved CEC (0.08 (0.17) vs (-0.009 (0.19); P =0.008) and neutrophil counts (-0.45 (-1.36- -0.45) vs -0.14 (-0.60-0.42; P =0.004). Conclusion: Patients with more neutrophils had lower CEC and higher NCB. Further, CEC mediates the relationship between neutrophils and NCB, underscoring the relationship between neutrophils and CEC in atherosclerosis.

Biological therapy in patients with psoriasis: What we know about the effects on renal function.

Psoriasis is a chronic inflammatory dermatosis affecting 2%-3% of the general population. The link between psoriasis and renal dysfunction has been investigated, demonstrating a common pro-inflammatory pathogenesis. This study is aimed at evaluating renal function in patients with moderate-to-severe chronic plaque psoriasis treated with biological therapy. We analyzed 92 patients, correlating PASI and serum creatinine levels at baseline, after 6 months and after 1 year of continuous treatment with biological therapy. Data were analyzed using paired t-test and the linear mixed model for PASI and serum creatinine levels correlation, whereas the analysis of variances (ANOVA) was used for creatinine levels assessment between the baseline, the 6-months and, 1-year later evaluation. We observed a significant mean decrease in comparing serum creatinine levels after 1 year of biological therapy (p < 0.001). Interestingly, PASI reduction is correlated with creatinine decrease, and the renal function improvement is greater when complete psoriasis remission is attained. Our data suggest that a drop in systemic inflammation, secondary to biological therapy administration, might improve renal function. Future research is needed to confirm and expand our findings.

Association of neutrophil-to-lymphocyte ratio with non-calcified coronary artery burden in psoriasis: Findings from an observational cohort study

BackgroundInflammation in the form of elevated high-sensitivity c-reactive protein (hs-CRP) has been shown to be critical in the development of atherothrombosis. Psoriasis, a chronic inflammatory skin disease, is associated with high systemic-inflammation, elevated neutrophil-to-lymphocyte ratio (NLR) and accelerated non-calcified coronary artery burden (NCB) by coronary computed tomography angiography (CCTA). We hypothesized that NLR would associate with early, rupture-prone atherosclerosis assessed as NCB independent of hs-CRP. Methods316 consecutive psoriasis participants were recruited with 233 having one-year follow-up as part of a prospective, observational cohort study design. CCTA scans were performed to assess NCB in all three major epicardial coronary arteries. ResultsPatients with above average NLR (>mean: 2.29 ​± ​1.21) were older (mean ​± ​SD; 52.0 ​± ​12.8 vs. 47.9 ​± ​12.6, p ​= ​0.002), had higher hs-CRP (med. IQR: 2.3 (0.9–7.3) vs. 1.4 (0.7–3.2), p ​= ​0.001) and had higher NCB (mean ​± ​SD; 1.21 ​± ​0.58 vs. 1.13 ​± ​0.49, p ​= ​0.018) when compared to patients with below average NLR. NLR associated with psoriasis area severity index score (β ​= ​0.14, p ​= ​0.017), hs-CRP (β ​= ​0.16, p ​= ​0.005), as well as NCB independent of traditional risk factors, body mass index, statin use and hs-CRP (β ​= ​0.08, p ​= ​0.009). One year of biologic therapy for psoriasis was associated with a reduction in NLR (−14.5%, p ​< ​0.001), and this change in NLR associated with change in NCB in fully adjusted models and beyond hs-CRP (β ​= ​0.17, p ​= ​0.002). ConclusionNLR associated with psoriasis severity, hs-CRP and NCB at baseline. Biologic therapy reduced NLR over time and this change in NLR associated with the change in NCB at one-year. Taken together, these findings suggest that NLR may capture psoriasis patients at higher risk of NCB due to residual inflammation not fully captured by hs-CRP.

P024 Treatment patterns of biologic therapies used to treat ulcerative colitis: A retrospective database analysis in the United States

BACKGROUNDs: Treatment goals for ulcerative colitis (UC) focus on inducing a response and maintaining long-term disease remission. The current study sought to document the real-world treatment patterns during the first year of biologic therapy in the United States. METHODS: This retrospective analysis used the PharMetrics Plus claims data from January 1, 2013 to October 1, 2017. Biologic-naïve patients aged ≥18 years with UC (ICD9:556.* or ICD10 K51.*) who newly initiated biologic therapy (adalimumab [ADA], infliximab [IFX], vedolizumab [VEDO], golimumab [GOL]) were included. Patients had to have 12 months of continuous enrollment prior to (pre-index) and after (post-index) their first biologic drug claim (index). Patients with Crohn's disease or a history of biologic therapy in the pre-index period were excluded. Treatment patterns were reported descriptively, including combination therapy (frequency of an IM with a biologic), persistence (frequency of patients using their index therapy at the end of the 12-month post-index period without a 60-day gap), and adherence (calculated based on the proportion of days covered). RESULTS: A total of N = 3,595 patients with UC were included (51.7% male; age = 42.4 years [SD = 13.6]; disease duration = 1.3 years [SD = 1.0]) with the following treatments at index: N = 2,055 on ADA, N = 1,218 on IFX, N = 152 on GOL, and N = 170 on VEDO. Use of a concomitant IM therapy at index occurred as follows: ADA = 30.75%, IFX = 32.10%, GOL = 29.61%, and VEDO = 25.29%. A total of 59.2% of patients who initiated a biologic therapy remained persistent (i.e., continued on therapy) throughout the 12-month post-index observation period. This varied by therapy: ADA = 56.2%, IFX = 64.9%, GOL = 44.1%, and VEDO = 69.4%. Non-persistent patients predominantly discontinued without switching to another medication or restarting their original medication (discontinuation rates ranged from 42.3% to 52.7% among ADA, GOL, and IFX patients). However, non-persistent VEDO patients predominantly restarted the same therapy after a ≥60 day discontinuation period (36.5%). Switching therapies immediately (i.e., less than 60 days) was also common across each treatment (ADA = 27.1%, IFX = 31.2%, GOL = 31.0%, VEDO = 28.9%). Adherence to biologic therapy, measured by the proportion of days covered, were as follows: ADA = 0.72, IFX = 0.81, GOL = 0.69, VEDO = 0.84. CONCLUSION(S): For UC patients initiating biologic therapy, at least 25% initiated concomitant IM therapy. A significant number (40%) of patients discontinued their biologic therapy within the first 12 months. These findings suggest a number of patients experience suboptimal levels of disease control within the first year of biologic therapy.

Clinical Impact of Sonographic Transmural Healing After Anti-TNF Antibody Treatment in Patients with Crohn's Disease.

To assess the clinical benefits of transmural healing (TH) shown on intestinal ultrasound (IUS) after treatment with tumor necrosis factor-alpha antibodies (anti-TNF) in patients with Crohn's disease. This prospective study included consecutively 36 patients who underwent IUS in the week prior to start anti-TNF treatment, at 12weeks, and 1year after starting treatment. The clinical response to treatment was assessed using the Crohn's disease activity index and C-reactive protein (CRP) values. TH was defined as the normalization of bowel wall thickness on IUS. Treated patients were considered to have a good outcome if none of the following situations presented: need to reintroduce corticosteroids or intensify maintenance therapy and/or need for surgery. After the induction regimen, 29 patients (80.6%) achieved clinical remission, and serum CRP values returned to normal in 20 patients (55.6%). In the IUS at 12weeks, treatment induced a statistically significant reduction in the wall thickness (p < 0.001) and color Doppler grade (p < 0.001), as well as resolution of complications in 66.7% of patients (p < 0.03). IUS after 1year of biological therapy showed TH in 14/33 patients (42.4%). During the follow-up (median 48.5months), 23 of the 33 (69.7%) patients in remission or response after induction therapy presented a good outcome. Sonographic TH was significantly related with better outcomes, with only 1/14 patients having a poor outcome compared to 9/19 without TH (OR 11.7, 95% CI 1.2-108.2 p = 0.01, Chi-squared test). Patients who achieve TH on IUS with biological treatment have better clinical outcomes.

INDIСATORS OF THE LYMPHOCYTE SUBSETS AS EFFICICIENCY PREDICTORS OF THERAPY WITH INHIBITORS OF TNFα IN CHILDREN WITH INFLAMMATORY BOWEL DISEASE

(IBD), who were for the first time treated with TNFα blocker (infliximab). Our aim was to determine prognostic informative value of the immunological parameters in order to assess the treatment efficiency. A comprehensive research included seventy children with IBD from 12 to 18 years old in the course of specific treatment (49 children with CD, 21 children with UC).The comparison group consisted of fifty healthy children of similar age who were subjected to a similar detailed examination. The patients were divided into two groups, depending on their therapeutic response following 1 year of biological therapy: the first group showed a persistent positive effect of the drug, and the second group exhibited only unstable effects of the treatment. We determined the contents of major and small subpopulations of peripheral blood lymphocytes before the first administration of infliximab. Immunophenotyping was performed by multicolor flow cytometry (FC 500), using the CD45, CD3, CD4, CD8, CD19, CD16, CD56, HLA-DR, CD5, CD161, CD127, CD25, and CD294 markers.We have revealed that the content of B lymphocytes was significantly reduced in children with unstable effects of therapy. By contrast, the B lymphocyte levels in children with persistent positive therapeutic effect did not differ from the comparison group. Analysis of the composition of the B lymphocyte profile showed an imbalance in the B1-to-B2 cell ratio, with decreased of B1 cell counts in IBD patients against the comparison group. In addition, the patients with unstable therapeutic effect showed a significant decrease in B2 cell numbers compared with a group with persistent effect and comparison group. The numbers of NK cells in IBD patients were found to be reduced against the comparison group. Assessment of T lymphocytes subsets revealed a number of features in the patients with minimal therapeutic effects, i.e., an increased level of activated T helper cells (CD4+CD25+CD127high) and Th17 lymphocytes (CD3+CD4+CD161+), as compared to children with stable effect of treatment and to the comparison group. Moreover, in children with minimal effects of therapy, the levels of Tregs within T-helper cell subsets were significantly higher than in the comparison group. By means of ROC analysis, we have identified most informative parameters for the groups with minimal versus persistent therapeutic effect, and showed a good quality for a discrimination model involving relative amount of Th17 cells, activated T helper cells and B lymphocytes. The number of Тh17 lymphocytes (% CD3+CD4+ lymphocytes) allowed to predict the effect of therapy with a TNFα blocker with high probability. The present study enables us to propose cellular immunity testing, as a promising tool for monitoring clinical state of IBD patients.

Utilization of Biologics in Saskatchewan

Background Few details are available about the factors driving cost increases of biologic medications. Objectives To describe trends in utilization and cost of biologic agents using administrative databases in Saskatchewan, Canada. Methods Two analyses were conducted. First, aggregate utilization of biologics based on prescriptions dispensed was measured in each calendar year between 2001 and 2013. Second, a retrospective cohort of new biologic users was created to examine trends in spending between 2001 and 2013. During the first year of biologic therapy, biologic cost was quantified for each specific biologic agent as: (a) total spending; (b) total mil - ligrams dispensed; and (c) estimated unit cost (i.e., total cost in 2013 $CAD divided by total milligrams dispensed during the year). Data analyses were descriptive and all biologic costs were adjusted to 2013 dollars (CAD). Results In the first year of biologic availability in Saskatchewan (2001), 133 patients were dispensed at least one biologic agent for a total cost of $0.5 million. In 2013, 2,402 biologic recipients were identified for a total cost of $51.8 million. Almost all of these biologic costs (88.9%) were paid by the provincial government. In 2013, infliximab was the most frequently used agent, accounting for 46.5% of all spending on biolog - ics. Infliximab was also the most expensive agent in 2013 (mean cost $31,340 ± 15,307) and showed the highest increase in the mean yearly cost over time due to greater quantities dispensed. Conclusion Biologic utilization will require ongoing monitoring to optimize patient-level and societal-level benefits.

Cost and effectiveness of biologics for rheumatoid arthritis in a commercially insured population.

Administrative claims contain detailed medication, diagnosis, and procedure data, but the lack of clinical outcomes for rheumatoid arthritis (RA) historically has limited their use in comparative effectiveness research. A claims-based algorithm was developed and validated to estimate effectiveness for RA from data for adherence, dosing, and treatment modifications. To implement the claims-based algorithm in a U.S. managed care database to estimate biologic cost per effectively treated patient. The cohort included patients with RA aged 18-63 years in the Optum Research Database who initiated biologic treatment between January 2007 and December 2010 and were continuously enrolled 6 months before through 12 months after the first claim for the biologic (the index date). Patients were categorized as effectively treated by the claims-based algorithm if they met all of the following 6 criteria in the 12-month post-index period: (1) a medication possession ratio ≥ 80% for subcutaneous biologics, or at least as many infusions as specified in U.S. labeling for intravenous biologics; (2) no increase in biologic dose; (3) no switch in biologics; (4) no new nonbiologic disease-modifying antirheumatic drug; (5) no new or increased oral glucocorticoid treatment; and (6) no more than 1 glucocorticoid injection. Drug costs (all biologics) and administration costs (intravenous biologics) were obtained from allowed amounts on claims. Biologic cost per effectively treated patient was defined as total 1-year biologic cost divided by the number of patients categorized by the algorithm as effectively treated with that index biologic. Sensitivity analysis was conducted to examine the total health care costs per effectively treated patient during the first year of biologic therapy. A total of 5,474 individuals were included in the analysis. The index biologic was categorized as effective by the algorithm for 28.9% of patients overall, including 30.6% for subcutaneous biologics and 22.1% for intravenous biologics. The index biologic was categorized as effective in the first year for 32.7% of etanercept (794/2,425), 32.3% of golimumab (40/124), 30.2% of abatacept (89/295), 27.7% of adalimumab (514/1,857), and 19.0% of infliximab (147/773) patients. Mean 1-year biologic cost per effectively treated patient, as defined in the algorithm, was lowest for etanercept ($43,935), followed by golimumab ($49,589), adalimumab ($52,752), abatacept ($62,300), and infliximab ($101,402). The rank order in the sensitivity analysis was the same, except for golimumab and etanercept. Using a claims-based algorithm in a large commercial claims database, etanercept was the most effective and had the lowest biologic cost per effectively treated patient with RA.

FRI0071 Effect of Biological Therapy on Fatigue in Patients with Rheumatoid Arthritis

BackgroundFatigue is a frequent symptom among patients with rheumatoid arthritis (RA) and contributes to decreased quality of life in these patients [1].There are various questionnaires to assess fatigue in rheumatic...

Gain in Quality-adjusted Life-years in Patients with Rheumatoid Arthritis During 1 Year of Biological Therapy: A Prospective Study in Clinical Practice

<b>Objective:</b> To assess the safety of government versus non-government public road transportation. <b>Design:</b> Descriptive study. <b>Setting:</b> Kandy Municipality Area, Sri Lanka. <b>Subjects:</b> All road traffic crashes reported to the Kandy Police from 1 October 1998 to 30 September 1999. <b>Main outcome:</b> Involvement in a road traffic crash reported to the Kandy Police in which a government bus, private bus, or a three-wheeler was involved. <b>Results:</b> During the study period, 132 government buses, 243 private buses, and 115 three wheelers were involved in 437 police reported road crashes. Of these crashes, eight (1.8%) were fatal and 132 (30.2%) were crashes resulting in injury requiring hospitalization. The majority of road crashes involved vehicle-vehicle interaction (63.4%) and vehicle-pedestrian interaction (17.8%), while the remainder consisted of vehicle-passenger and vehicle-road structure crashes. The research highlights an increased risk associated with travel on privately owned buses (RR = 2.0, 95% CI 1.6 to 2.5) and three wheelers (RR = 2.2, 95% CI 1.7 to 2.8) compared to travel on government buses. The disparity in crash rates between government and privately owned transportation modes can be explained, in part, by fewer safety requirements being imposed on the deregulated public transportation system. <b>Conclusions:</b> Recommendations are made in order to address the differential in crash rates between public and private vehicle ownership used for public transportation in Sri Lanka.

Gain in Quality-adjusted Life-years in Patients with Rheumatoid Arthritis During 1 Year of Biological Therapy: A Prospective Study in Clinical Practice

The quality-adjusted life-year (QALY) is used to measure outcome in rheumatoid arthritis (RA) studies; identification of drivers of a gain in QALY might help predict a treatment response. We investigated how changes in components of the Disease Activity Score-28 joints (DAS28) were associated with the European League Against Rheumatism (EULAR) and European Quality of Life 5 Dimensions (EQ-5D) responses; and what baseline variables predicted the change in QALY following 1 year of biological therapy. Data were collected at baseline and after 3, 6, and 12 months of biological therapy in Danish patients with RA and included bDAS28, sociodemographic data, comorbidity, Health Assessment Questionnaire (HAQ), and EQ-5D scored using the Danish algorithm. A cross-tabulation based on EULAR versus EQ-5D responses was performed, and the association of each DAS28 component across the EULAR/EQ-5D response groups was tested. Predictors of a change in QALY were assessed in a multiple regression model including baseline clinical and patient-reported data as explanatory variables. In total, 315 patients entered the study; 77% were women, 78% IgM rheumatoid factor-positive, with mean age 55 (SD 13) years, disease duration 10 (SD 8) years, mean DAS28 4.9 (SD 1.2), HAQ score 1.22 (SD 0.70), and EQ-5D score 0.60 (SD 0.19). Sixty-eight percent of patients gained QALY; the mean gain was 0.14 (SD 0.13). The patient global score was strongly correlated with both EULAR and EQ-5D responses. The gain in QALY increased with increasing patient global score and number of swollen joints, but not with C-reactive protein (CRP). The subjective patient global score was the best baseline predictor of gain in QALY following biological therapy, while the objective CRP measure had no predictive value. It seems that no sharp demarcation between objective and subjective measures could be determined.

AB0304 Predictors of gain in quality adjusted life years in RA patients treated with biologics for one year

BackgroundThe Quality Adjusted Life Year (QALY), based on health-related quality of life measures such as euroqol 5 dimensions (EQ-5D), is an important outcome in rheumatoid arthritis (RA) studies, as it...

AB0293 Changes in glucocorticoid treatment in the first year of biological therapy in RA patients

BackgroundGlucocorticoids (GC) are very commonly used in the rheumatoid arthritis (RA) treatment; however their potential risks warrants a rational use. 1,2ObjectivesEvaluate the impact of biological therapies on GC use in...

SAT0452 Response matters in rheumatoid arthritis: improvements in patient resource use, activities of daily living and employment are only significant if remission is achieved

BackgroundImproved productivity has been observed for rheumatoid arthritis (RA) patients achieving a good response with anti-TNF therapy. We hypothesized that the magnitude of improvement in patient-level resource use indicators may...

Su1220 Dose Optimization Is Effective in Patients With Ulcerative Colitis Losing Response to Infliximab: A Collaborative Multicentre Retrospective Study

Background: The new therapeutic goal in patients with Crohn’s disease (CD) is long term mucosal healing, due to its proven association with better outcome (better quality of life, fewer complications, less hospitalization). Not all CD patients treated with biologics achieve deep remission and in those patients that achieve it, it can be shortly lived. The aim of our study was to assess the frequency and durability of deep remission in CD patients on biological treatment in a clinical setting. Methods: All CD patients treated with biologics in our department were followed prospectively. Demographical data (age, sex), disease characteristics (Montreal classification, time between diagnosis and start of biological therapy, previous surgeries), type of biologic therapy, other treatments, endoscopic findings were noted. All patients had ileocolonoscopy performed at 6 12 months interval. Deep remission was defined when both clinical (CDAI <150) and endoscopic (no ulcers) remissions were achieved. Results: 49 CD patients, mean age 37±13.06 (20 65) years were followed for a median of 38 (12 72) months. Localization of the disease was ileal in 12.24%, ileocolonic in 32.65% and colonic in 55.1% patients, with 26.53% having associated perianal fistulas. Mean time from diagnosis till biologic therapy was started was of 4.83±4.66 (0 18) years. The majority of patients (41) received Infliximab, the rest Adalimumab. Mean treatment time with biologics was 30.57±15.73 (12 72) months. During this time a mean number of 5.36 (2 11) ileocolonoscopies were performed per patient. Deep remission was achieved in 79.6% of cases after a mean of 8.23±7.52 (2 36) months and was sustained in 51.28% of cases. 48.71% of patients lost deep remission after a mean time of 12±6.48 (3 30) months. In 42.10% of cases (8 patients) after 8.25±3.1 months deep remission was induced again: in 5 cases with biologic dose escalation +/ immunosupressor, one with local budesonide treatment and in 2 cases (with clinical remission) spontaneous healing of ulcerations was observed at follow up ileocolonoscopies, without any therapeutic intervention. Conclusions: In clinical setting deep remission can be achieved in a great proportion of patients after a variable time interval, sometimes over one year of biologic therapy. In patients with flares while on biologic treatment deep remission can be re induced with various therapeutic strategies. Our study showed that transitory, clinically silent, endoscopic relapse is possible during biologic maintenance therapy. P549 Dose optimization is effective in patients with ulcerative colitis losing response to infliximab: a collaborative multicentre retrospective study M. Cesarini1 *, K. Katsanos2, P. Ellul3, P. Lakatos4, K. Papamichael5, F. Caprioli6, E. Tsianos2, G. Mantzaris5, S. Danese7, G. Fiorino7. 1Sapienza University of Rome, Medicina Interna e Specialita Mediche, Rome, Italy, 2University of Ioannina, Greece, 3Mater Dei Hospital, Malta, 4Semmelweis University, Budapest, Hungary, 5Evangelismos Hospital, Athens, Greece, 6University of Milan, Italy, 7 IRCCS Humanitas, IBD Center, Rozzano, Italy