Impact Of Biologic Therapy Research Articles

P131 NATIONAL TRENDS IN HOSPITALIZATION, SURGICAL RESECTION, AND COMORBIDITIES IN PEDIATRIC INFLAMMATORY BOWEL DISEASES

Abstract Background Therapeutic options for pediatric inflammatory bowel disease (PIBD) have dramatically changed over the last decades with the widespread use of biologic medications. However, the overall impact of biologic therapy on PIBD outcomes (specifically hospitalizations, comorbidities, surgical rates, and postoperative complications) remains unclear. We aimed to fill this gap in the literature by using a large, validated, national database, to study the change in outcomes over the last decade. We hypothesized that morbidity in pediatric IBD has decreased over time with the increased use of biologic therapy. Methods The National Inpatient Sample (NIS) Database and ICD-9-CM codes were utilized to identify inpatient admissions with a primary or secondary diagnosis of pediatric Crohn’s disease (CD) or ulcerative colitis (UC) from 2002–2015. Trends in hospitalizations, comorbidities (including malnutrition and weight loss), surgical procedures, and post-operative complications were examined using joinpoint regression analysis. Results There were 119,282 admissions for PIBD during the study period. The annual incidence of hospitalization increased significantly over time for both CD (average annual percent change [AAPC] 6.0%, 95%confidence interval [CI] 4.7, 7.2) and UC (AAPC 7.2%, 95% CI 6.2, 8.1). The rate of intestinal resection decreased in CD patients (AAPC -6.4%, 95%CI, -8.7, -4.1) while postoperative complications remained unchanged. However, comorbidities increased significantly in CD patients (AAPC 6.8%, 95%CI, 4.6, 9.0). For pediatric UC patients, postoperative complications (AAPC 6.7%, 95%CI, 1.2, 12.4), and comorbidities (AAPC 10.2%, 95%CI, 8.8–11.6) increased significantly over time while intestinal resection rates remained stable. Conclusions Intestinal resection rate in pediatric CD has decreased over time, but not in pediatric UC. Annual incidence of hospitalization and comorbidities continue to increase in PIBD despite the increased availability and use of biologic medications. Our findings emphasize the critical need for prevention and novel therapeutic options for this vulnerable patient population.

Sa1861 – Impact of Biologic Therapy on Resolution of Fatigue Symptoms in Patients with Active Inflammatory Bowel Disease: A Prospective Cohort Study

Sa1861 – Impact of Biologic Therapy on Resolution of Fatigue Symptoms in Patients with Active Inflammatory Bowel Disease: A Prospective Cohort Study

Impact of biological therapy on work outcomes in patients with axial spondyloarthritis: results from the British Society for Rheumatology Biologics Register (BSRBR-AS) and meta-analysis

ObjectivesTo quantify, among patients with axial spondyloarthritis (axSpA), the benefit on work outcomes associated with commencing biologic therapy.MethodsThe British Society for Rheumatology Biologics Register in Axial Spondyloarthritis (BSRBRAS) recruited patients...

K2 Impact of biologic therapy on work in patients with axial spondyloarthritis: results from the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis (BSRBR-AS) and meta-analysis

K2 Impact of biologic therapy on work in patients with axial spondyloarthritis: results from the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis (BSRBR-AS) and meta-analysis

Impact of biological therapy on body composition of patients with Chron's disease.

Protein-energy malnutrition in Crohn's disease (CD) has been reported in 20 to 92% of patients, and is associated with increased morbidity and mortality and higher costs for the health system. Anti-TNF drugs are a landmark in the clinical management, promoting prolonged remission in patients with CD. It is believed that the remission of this disease leads to nutritional recovery. The effect of biological therapy on body composition and nutritional status is unclear. Prospective study of body assessment by bioelectrical impedance method in patients with moderate to severe CD undergoing treatment with infliximab. The main outcome was the body composition before and after 6 months of anti-TNF therapy. There was a predominance of females (52%) with a mean age of 42±12 years. Most patients were eutrophic at baseline and remained so. There was an increase in all parameters of body composition after anti-TNF treatment: BMI (22.9±3.2 versus 25±3.8; p=0.005), waist circumference (88.1±6.7 versus 93.9±7.7; p=0.002), lean mass index (17.5±2.2 versus 18.2±2.3; p=0.000) and fat mass index (5.5±2.3 versus 6.8±2.3; p=0.000). Phase angle remained unchanged (6.2 versus 6.8; p=0.94). After therapy with IFX, all components of body composition increased, except for phase angle. The substantial increase in fat mass index and waist circumference led to concern regarding cardiovascular risk and, thus, to the need for further studies.

Impact of biologic therapies on risk of major adverse cardiovascular events in patients with psoriasis: systematic review and meta-analysis of randomized controlled trials.

SummaryConcerns have been raised regarding an increased risk of major adverse cardiovascular events (MACEs) (myocardial infarction, cerebrovascular accident or cardiovascular death) in patients treated with anti‐interleukin (IL)‐12/23 agents for moderate‐to‐severe psoriasis. We aimed to examine the risk of MACEs in adult patients with plaque psoriasis that are exposed to biologic therapies via a meta‐analysis of randomized controlled trials (RCTs). Data were obtained from systematic searches in the Cochrane Library, MEDLINE and Embase, U.S. Food and Drug Administration, European Medicines Agency, individual pharmaceutical companies online search platforms and five trials registers (up to 31 March 2016). We selected RCTs reporting adverse events in adults with plaque psoriasis receiving at least one licensed dose of biologic therapy, conventional systematic therapy or placebo. We calculated Peto odds ratios (ORs) with 95% confidence intervals (CIs) and calculated I 2 statistics to assess heterogeneity. Overall, 38 RCTs involving 18 024 patients were included. No MACEs were observed in 29 studies, while nine RCTs reported 10 patients experiencing MACEs. There was no statistically significant difference in risk of MACEs associated with the use of biologic therapies overall (OR 1·45, 95% CI 0·34–6·24); tumour necrosis factor‐α inhibitors (adalimumab, etanercept and infliximab) (OR 0·67, 95% CI 0·10–4·63); anti‐IL‐17A agents (secukinumab and ixekizumab) (OR 1·00, 95% CI 0·09–11·09) or ustekinumab (OR 4·48, 95% CI 0·24–84·77). No heterogeneity was observed in these comparisons. In conclusion, the limited existing evidence suggests that licensed biologic therapies are not associated with MACEs during the short randomized controlled periods in clinical trials.

What is the impact of biologic therapies on common co-morbidities in patients with rheumatoid arthritis?

Biologic therapies have revolutionised disease control in patients with rheumatoid arthritis (RA). Theoretically, they have the potential to influence co-morbid disease associated with RA through better control of systemic inflammation. Conversely, co-morbidity may occur as an adverse effect of the drugs. The latest evidence from observational data shows an increased risk of infection in the first 6 months of treatment with tumour necrosis factor inhibitor (TNFi) therapies and potentially other biologic therapies. Rates of infection after the first 6 months decrease and become comparable to patients with RA treated with conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs). TNFi also appear to reduce the risk of cardiovascular disease in these patients, in particular ischaemic heart disease. TNFi treatment may be associated with a small increase in the risk of developing squamous cell carcinoma of the skin; in terms of other cancers, rates appears to be no different to those seen in patients treated with csDMARDs. There is a paucity of data on the impact of other biologic therapies and the effect of all biologic therapies on other common co-morbidities.

P409. Impact of biological therapy in postoperative morbidity in elective surgical resections in Crohn’s disease

P409. Impact of biological therapy in postoperative morbidity in elective surgical resections in Crohn’s disease

Survival improvements associated with access to biological agents: Results from the South Australian (SA) metastatic colorectal cancer (mCRC) registry

Background Randomized controlled trials evaluating biological therapy have shown improvements in survival from metastatic colorectal cancer (mCRC). Subjects in the trials represent a selected proportion of mCRC patients. We have the potential to assess the impact of biological therapy on mCRC outcomes, particularly the effect of bevacizumab, from a population-based clinical registry by comparing two time cohorts with differences in therapy accessibility.Material and methods A retrospective cohort study was performed by analyzing the South Australian (SA) mCRC registry data based on diagnosis in two time periods: 1 February 2006–31 May 2009 (Cohort A) versus 1 June 2009–30 June 2014 (Cohort B). The demarcation for these cohorts was chosen to reflect the change in accessibility of bevacizumab from July 2009.Results Between February 2006 and June 2014, 3308 patients were identified through the SA mCRC registry: 1464 (44%) in Cohort A and 1844 (56%) in Cohort B. 61 and 59% patients in Cohort A and B, respectively received systemic therapy (p = 0.26). Major differences in clinical characteristics were: biological therapy use 18 versus 33% (p < 0.001) and clinical trial enrolment 12 versus 7% (p < 0.001). Uptake of bevacizumab was: first-line 9 versus 42% and second-line 6 versus 16%. Median overall survival (mOS) for the entire group was: 13.1 versus 17.1 months (HR 0.80; 95% CI 0.74–0.87). Evaluation restricted to patients receiving systemic therapy was 20.5 versus 25.2 months (HR 0.80; 95% CI 0.72–0.89). Multivariate analysis indicated that biological therapy and Cohort B were associated with improved mOS.Conclusion The expected rise in bevacizumab administration was observed in Cohort B. Its use in first-line therapy remained relatively low even after the reimbursement, potentially reflecting real world practice where comorbidities, primary in-situ and age may contraindicate its use. mOS improvement over time was attributed to increased access to biological therapy, especially bevacizumab and possibly advance in peri-operative and supportive care.

The Impact of Biological Therapy on Liver Transplant Outcomes in Pvvvatients With Primary Sclerosing Cholangitis and Inflammatory Bowel Disease

The Impact of Biological Therapy on Liver Transplant Outcomes in Pvvvatients With Primary Sclerosing Cholangitis and Inflammatory Bowel Disease

The impact of biologic therapy in chronic plaque psoriasis from a societal perspective: an analysis based on Italian actual clinical practice.

Psoriasis is one of the most common forms of chronic dermatitis, affecting 2-3% of the worldwide population. It has a serious effect on the way patients perceive themselves and others, thereby prejudicing their quality of life and giving rise to a significant deterioration in their psycho-physical well-being; it also poses greater difficulties for them in leading a normal social life, including their ability to conduct a normal working life. All the above-mentioned issues imply a cost for the society. This study proposes to evaluate the impact on societal costs for the treatment of chronic plaque psoriasis with biologics (etanercept, infliximab and adalimumab) in the Italian clinical practice. A prospective observational study has been conducted in 12 specialized centres of the Psocare network, located throughout Italy. Direct and indirect costs (as well as the health-related quality of life of patients with plaque psoriasis undergoing biologic treatments) have been estimated, while the societal impact has been determined using a cost-utility approach. Non-medical and indirect costs account for as much as 44.97% of the total cost prior to treatment and to 6.59% after treatment, with an overall 71.38% decrease. Adopting a societal perspective in the actual clinical practice of the Italian participating centres, the ICER of biologic therapies for treating plaque psoriasis amounted to €18634.40 per QALY gained--a value far from the €28656.30 obtained by adopting a third-party payer perspective. Our study confirms that chronic psoriasis subjects patients to a considerable burden, together with their families and caregivers, stressing how important it is to take the societal perspective into consideration during the appraisal process. Besides, using data derived from Italian actual practice, treatment with biologics shows a noteworthy benefit in social terms.

The impact of biological therapy on regulatory T cells in rheumatoid arthritis.

Regulatory T cells (Treg) are functionally defective in patients with RA. Restoring their function may not only control inflammation but also restore tolerance in these patients. Biologic therapies have been tremendously successful in treating RA. Here we review numerous reports suggesting that these immunomodulatory therapies have an impact on Treg and that this may contribute to their beneficial effects. Better understanding of their mode of action may not only lead to improvements in therapies and sustained remission but also enable the development of biomarkers of response, which would be the first steps towards personalized medicine.

Meta-analysis of outcomes of VEGF and EGFR targeted biologic therapy in relapsed metastatic colorectal cancer (mCRC).

534 Background: Biologic therapies used in treatment of mCRC are expensive and there is debate about their value. We examined the impact of biologic therapy on overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and grade 3/4 toxicity for patients beyond first-line treatment. Methods: MEDLINE, EMBASE, and Cochrane libraries were searched for randomized studies in relapsed mCRC comparing treatment containing targeted therapy to the same treatment without targeted therapy. Biologic agents were classed as: EGFR-inhibitors (EGFR-I), VEGF antibody/trap and VEGFR tyrosine kinase inhibitors (TKI). Only KRAS wild-type patients were included for EGFR-I analysis. Results were aggregated according to standard meta-analytic techniques. Results: 10 studies evaluating 5,847 patients were identified. Considering subgroups and lines, OS and PFS benefit was demonstrated in all groups across all lines except for OS in 2nd line EGFR-I use (which may be due to subsequent crossover). A benefit to ORR was seen with EGFR-I 2nd line (Pooled ORR benefit +24%, Odds Ratio (OR) 4.44, 95% CI 3.20-6.18), EGFR-I 3rd line and beyond (Pooled ORR benefit +16%), VEGF antibody/trap (Pooled ORR benefit +7.2%, OR 2.00, 95% CI 1.57-2.54) and VEGFR TKI (Pooled ORR benefit +1.9%, OR 2.05, 95% CI 1.27-3.30). The risk of grade 3/4 toxicity was greater with the addition of all targeted agents. Conclusions: The use of VEGF and EGFR targeted biologic agents beyond first-line setting in mCRC results in a benefit to OS, PFS and ORR for all agents except for OS benefit with second-line EGFR-I. This benefit comes at the cost of increased toxicity. [Table: see text]

Multidisciplinary and evidence-based management of fistulizing perianal Crohn's disease.

Perianal symptoms are common in patients with Crohn's disease and cause considerable morbidity. The etiology of these symptoms include skin tags, ulcers, fissures, abscesses, fistulas or stenoses. Fistula is the most common perianal manifestation. Multiple treatment options exist although very few are evidence-based. The phases of treatment include: drainage of infection, assessment of Crohn's disease status and fistula tracts, medical therapy, and selective operative management. The impact of biological therapy on perianal Crohn's disease is uncertain given that outcomes are conflicting. Operative treatment to eradicate the fistula tract can be attempted once infection has resolved and Crohn's disease activity is controlled. The operative approach should be tailored according to the anatomy of the fistula tract. Definitive treatment is challenging with medical and operative treatment rarely leading to true healing with frequent complications and recurrence. Treatment success must be weighed against the risk of complications, specially anal sphincter injury. A full understanding of the etiology and all potential therapeutic options is critical for success. Multidisciplinary management of fistulizing perianal Crohn's disease is crucial to improve outcomes.

The comparison of effects of biologic agents on rheumatoid arthritis damage progression is biased by period of enrolment: Data from a systematic review and meta-analysis

ObjectivesTo indirectly compare the 12-month effects of available biologic agents in slowing RA radiographic progression. MethodsA systematic review of literature of randomised, double-blind, controlled trials (RCTs) evaluating RA radiographic progression as end point was conducted using a PubMed searching of MEDLINE from January 1995 to May 2012. For each trial, the mean change from baseline of the standardised annual radiographic progression score (weighted for estimated annual progression rate) was estimated, and the effect size was calculated as the difference between biologic and non-biologic-treated groups. In order to optimise data homogeneity and improve RCTs comparison, a mixed-effect model was applied including previous responsiveness to methotrexate (MTX-experienced or MTX-naïve populations) and period of study enrolment as moderators. ResultsThe PubMed search resulted in 183 references, and 14 were eligible for the meta-analysis. The analysis of study distribution in forest plots showed a high correlation between the study period of enrolment and the impact of biological therapy in both MTX-naïve and MTX-experienced subgroups. In particular, effect size was the highest for older trials and progressively decreased in the most recent ones, suggesting a highest propensity to radiographic progression in populations enroled in older trials. Some statistically significant differences among RCTs were found in both subgroups but were significantly biased by the different propensity to radiographic progression due to period of enrolment. ConclusionsOur meta-analysis demonstrated that period of enrolment deeply influence study population propensity to radiographic progression in each trial. This finding does not allow the indirect comparison of various biologic agents, despite our mixed-model significantly reducing heterogeneity among RCTs.

Clinical impact of biologic therapy in the treatment of SLE

Biologic therapies have generated substantial research interest for treating autoimmune diseases, resulting in several US Food and Drug Administration approvals. However, clinical trial results in systemic lupus erythematosus (SLE) populations have failed to meet efficacy expectations, primarily owing to methodological flaws in design, especially outcome measures. To address these issues, the US Food and Drug Administration published a guidance document for clinical trial design in SLE that included specific efficacy endpoints for measuring disease severity. Belimumab was the first biologic approved for SLE based on positive responses measured with the SLE Responder Index, which required a decrease in inflammation, no new organ domains being involved, and improvement in physician global assessment. Trials of other biologics have used other versions of SLE Responder Index responder indices. In addition to belimumab, a score of other biologic agents are being investigated, primarily those targeting T cells, B cells, complement, and tolerogen-targeting agents. Their development stages and clinical trial results vary. Belimumab has generated the greatest amount of clinical trials, as investigators try to further define its role in clinical practice. Results have been shared in many forums, including annual meetings of the American College of Rheumatology and European League Against Rheumatism, along with publications in the medical literature. These findings indicate that belimumab is effective in patients with more active disease who are able to wait up to 3 months for improvement. Additionally, it can be considered for patients with active disease despite therapy with NSAIDs, antimalarials, immunosuppressives, or corticosteroids, especially if the benefits of treatment outweigh its risks or if the patient is intolerant to steroids or immunosuppressives. Additional file 1 contains an edited transcript of the full presentation.

THU0151 Disease Duration and Year of Publication Affect the Results of Studies on Rheumatoid Arthritis Damage Progression by Biologic Agents: A Systematic Review and Meta-Analysis

BackgroundDirect head-to-head comparisons among all available biologic agents for efficacy on damage progression in rheumatoid arthritis (RA) have not been conducted.ObjectivesTo indirectly compare the 12 months effects of available biologic...

Surgical Outcomes in Inflammatory Bowel Disease Patients and the Potential Impact of Biologic Therapies

The decision to proceed with surgery in an inflammatory bowel disease (IBD) patient is ideally a collaborative effort between the patient, gastroenterologist, and surgeon. Unlike emergency situations where surgery is required to address significant complications of the underlying disease, either ulcerative colitis (UC) or Crohn's disease (CD), elective cases often allow optimizing patient or disease factors in an attempt to improve surgical outcomes. Numerous factors contribute to success after IBD surgery. A detailed description of the pre-, intra-, and postoperative patient and procedure-specific risk factors associated with contributing to or reducing postoperative complications is beyond the scope of this monograph. However, a unique factor often encountered in IBD patients is their long-term immunosuppressive medication use in the perioperative period. They might be on a single agent. However, often they are on multiple medications with different modes of action. In this article, we will review the evidence regarding the impact of immunosuppressive medications commonly used in the treatment of IBD patients with an in-depth consideration of the newer antibody-based therapies.

Faecal diversion in the management of perianal Crohn’s disease

Severe perianal Crohn's disease remains an uncommon but important indication for faecal diversion (FD). The advent of biological therapy such as infliximab for Crohn's disease is considered to have improved the outcome for these patients. The aim of this study was to assess the outcome of patients undergoing FD for perianal Crohn's disease and the impact of biological therapy (infliximab). Retrospective chart review was undertaken of patients who underwent FD for management of perianal Crohn's disease at two tertiary centres between 1990 and 2007. Patient demographics, disease extent and use of biological therapy were recorded. Subsequent surgery was assessed. The impact of infliximab on rates of proctocolectomy and restoration of intestinal continuity was assessed. Twenty-one patients (one male, 20 female), median age 34 years (range 21-67 years), underwent FD for perianal Crohn's disease. At a median follow-up time of 22 months (range 4-121 months), four patients had undergone stoma closure, 11 had had proctocolectomy and six had a stoma in situ. The effects of the procedure on severity of perianal disease were no effect in four (19%), temporary improvement in six (29%), initial improvement with later plateau in seven (33%) and healing in four patients (19%). Eleven patients (52%) received infliximab. In this group, four underwent proctocolectomy and two had intestinal continuity restored. This was not significantly different from the noninfliximab group. Patients undergoing FD for perianal Crohn's disease have <20% likelihood of restoration of intestinal continuity. This is not improved with biological therapy.

Deficiencies in current evaluations of the cost-effectiveness of biologic agents for RA

The impact of biologic therapy for rheumatoid arthritis on quality of life has clear relevance to studies of the cost-effectiveness of these agents. As discussed in this Viewpoint, however, several deficiencies in current economic evaluations need to be overcome in order to enhance the utility of such research.