Objectives: To identify the predictors of switching from the first biologic to a second biologic in rheumatoid arthritis (RA) patients newly initiated on biologic treatments. Methods: Adult RA patients (18-64 years old) initiated on adalimumab, etanercept, infliximab, certolizumab, golimumab, abatacept, rituximab, tocilizumab, or anakinra between 2009 and 2011 were identified using a commercial claims database. Switching patterns were examined within one year after biologic initiation using descriptive statistics. Health care resource utilization (HCRU) variables (the number of 30-day supplies for steroid and DMARDs, and the claim counts for RA-related outpatient visits, radiographic, laboratory, intra-articular injections, rehabilitation, and surgical procedures) were assessed within one year prior to the switch date for switchers or the end of the study period for non-switchers. Pairwise comparisons of patient characteristics and HCRU variables were conducted using t-tests, Mann-Whitney U tests, and Chi-squared tests. Multiple logistic regressions were used to identify HCRU predictors of switching. Results: A total of 12,370 patients were included in the analysis. The switch rate within one year after biologic initiation was 18.4%, and the median time to switch was 181 days. More females switched compared to males (19.2% vs. 15.9%, p<.001). Switch rates were also higher in patients started on anti-TNFs compared to non-anti-TNFs (19.2% vs. 12.0%, p<.001). Furthermore, switch rates were highest in patients started on golimumab (21.0%) and were lowest in patients started on rituximab (4.8%). Overall, switchers had significantly higher rates and quantities of RA-related HCRU than non-switchers, except in the use of surgical procedures. Logistic regression models revealed that all the HCRU variables were significant predictors of switching, and patients on infliximab, abatacept, tocilizumab, and rituximab had significantly lower odds of switching than patients on etanercept. Combination therapy with DMARDs was also significantly associated with lower odds of switching. Conclusion: Switching of biologics is common in RA patients initiated on biologic therapy. There are marked differences in demographic characteristics and HCRU patterns between switchers and non-switchers. This study demonstrates that patterns of RA-related HCRU can be used to predict switching and thus can potentially serve as useful measures of treatment ineffectiveness. / text

Biological and therapeutic agents are used in food animal production to maintain animal health and well being, prevent and treat disease, and to maintain or enhance production. Concerns about the use of pharmaceutical agents in food animal production have been raised, especially in relation to food quality and safety. This study addressed the scarcity of information concerning the quantity of pharmaceuticals being used and the reasons for their use in sheep production. Additional goals included determining the sources of information used by shepherds in making treatment decisions and evaluating the economic impact that pharmaceutical usage has on sheep production. Thirty-nine Virginia sheep producers participated in this study of four months duration from March through September. After completing an initial questionnaire to determine flock and management characteristics, participants were asked to record all treatments with biological and therapeutic agents that occurred within their sheep flocks. A total of 14,310 treatments were recorded for a median of 1.5 treatments per sheep per month. Parasite control and vaccination were the most frequent reasons for treatment (64.9% and 15.2%, respectively) with vitamin/mineral supplementation being the next most common (8.8%). Price information was collected for 13,912 treatment events. An estimated total of $7,523.78 was spent on pharmaceutical treatment over the course of the study. This amounts to a cost of $0.63 per sheep per month of observation. Results of this study will enhance the ability of producers to evaluate treatment decisions, allow comparisons to be made between operations and provide a base of information for future research. / Master of Science

Biologics — biomolecule-based therapeutics — are predicted to become the next generation of therapeutical drugs. The pharmaceutical industry is investing a great amount of money into research in this medical field, which shows the importance and the need of analyses regarding biological drugs. This report is a survey of commercial biologics in which the market and trends regarding the past, present and future are analysed. The results are based on a literature study limited to commercial biologics — either as chemical entities, as conjugates to another class of biomolecules or as medical devices. The market for biomolecule-based therapeutics and medical devices is predicted to flourish as the new generations of peptides, proteins, oligonucleotides, carbohydrates and lipids increase in both approvals and sales. The fact that scientists have gained a broader comprehension on a molecular level due to advanced technologies has resulted in biologics reaching clinical maturity. The optimized pharmacokinetic properties, greater specificity, and the increased therapeutic window have led to reduced side effects compared to traditional therapeutical alternatives. Due to new development approaches — peptidomimetics — the stability of peptides has shown to increase. This results in a huge market and development potential. The protein therapeutics market is the largest among biologics, and their subgroup — the monoclonal antibody-based therapeutics market — is the fastest growing. With a high growth rate of novel therapeutics in development, the market will continue to expand. Conjugated monoclonal antibodies (ADC) and GalNAc conjugates to small interfering RNA are just a few examples of high potential drugs that are expected to increase on the market and in clinical development. Oncology is the dominating therapeutic area, where great success has been observed in both clinical and pre-clinical studies. Lipid conjugates have proven to be efficient in the treatment of tumour cells and the cytotoxic ADC grant great hope for the biomolecule-based therapeutics market. The market is also expected to grow for establishing biologics; for example the increasing need of anticoagulants is predicted to double the Heparin market to 2023 and the demand for novel treatment alternatives opens market opportunities for Heparin biosimilars. The biological vaccine market is also predicted to grow together with biologics, as mutated animal-spread diseases increase in number.

Biologics — biomolecule-based therapeutics — are predicted to become the next generation of therapeutical drugs. The pharmaceutical industry is investing a great amount of money into research in this medical field, which shows the importance and the need of analyses regarding biological drugs. This report is a survey of commercial biologics in which the market and trends regarding the past, present and future are analysed. The results are based on a literature study limited to commercial biologics — either as chemical entities, as conjugates to another class of biomolecules or as medical devices. The market for biomolecule-based therapeutics and medical devices is predicted to flourish as the new generations of peptides, proteins, oligonucleotides, carbohydrates and lipids increase in both approvals and sales. The fact that scientists have gained a broader comprehension on a molecular level due to advanced technologies has resulted in biologics reaching clinical maturity. The optimized pharmacokinetic properties, greater specificity, and the increased therapeutic window have led to reduced side effects compared to traditional therapeutical alternatives. Due to new development approaches — peptidomimetics — the stability of peptides has shown to increase. This results in a huge market and development potential. The protein therapeutics market is the largest among biologics, and their subgroup — the monoclonal antibody-based therapeutics market — is the fastest growing. With a high growth rate of novel therapeutics in development, the market will continue to expand. Conjugated monoclonal antibodies (ADC) and GalNAc conjugates to small interfering RNA are just a few examples of high potential drugs that are expected to increase on the market and in clinical development. Oncology is the dominating therapeutic area, where great success has been observed in both clinical and pre-clinical studies. Lipid conjugates have proven to be efficient in the treatment of tumour cells and the cytotoxic ADC grant great hope for the biomolecule-based therapeutics market. The market is also expected to grow for establishing biologics; for example the increasing need of anticoagulants is predicted to double the Heparin market to 2023 and the demand for novel treatment alternatives opens market opportunities for Heparin biosimilars. The biological vaccine market is also predicted to grow together with biologics, as mutated animal-spread diseases increase in number.

Psoriasis is a chronic, immunological and systemic disease with an estimated prevalence of about 2-3 percent. Psoriasis is associated with the joint disease psoriasis arthropathy. There are several treatments options available for psoriasis and patients with moderate to severe psoriasis generally need systemic agents. In 2004 biologics were introduced for patients with moderate to severe psoriasis in Sweden. The overall objective of this thesis was to assess the relationship between Health Related Quality of Life (HRQOL) and clinical outcome measures in psoriasis patients, to analyse the effectiveness of biologics in psoriasis in everyday clinical practice and to explore how costs of the psoriasis population changed after the introduction of biologics in Sweden. Methods: Research was based on national administrative registers and PsoReg, the Swedish registry for systemic treatment of psoriasis. In a cross-sectional study (paper I) the three outcome measures: the generic HRQOL measure EQ-5D, the dermatology specific HRQOL measure the Dermatology Life Quality Index (DLQI) and the clinical measure of skin involvement, Psoriasis Area and Severity Index (PASI), were analysed by demographic characteristics. The generic EQ-5D among psoriasis patients was compared to previously published values for the general population in Sweden. Relationships between measures were examined with correlation tests and regression analysis. A longitudinal study included patients registered in PsoReg who switched to a biologic agent for the first time during registration (paper II). The three outcomes EQ-5D, DLQI, and PASI were analysed before and after switch in the overall patient group and in subgroups. The relative effectiveness of continuing with the standard care of conventional treatment compared to switching from standard care to biologics was analysed in patients with moderate to severe psoriasis (paper III). Patients in PsoReg were matched with propensity scores and average treatment effects were estimated. The estimated outcomes were the change of EQ-5D, DLQI, and PASI. Patients were identified in national registers at the National Board of Health and Welfare when analysing costs; either by a registration of a psoriasis diagnosis in the national patients register and/or by a registration in the prescribed drugs register of a topical treatment with calcipotriol, a substance which has the indication psoriasis only (paper IV). Direct costs included patients’ visits in specialist health care and prescribed drugs used for psoriasis treatment, retrieved from the national patients register and the prescribed drugs register, respectively. Indirect costs included productivity loss in terms of sick leave and disability pension, which estimated as excess costs compared to controls. Controls were selected from the normal population and matched on sex, age and municipality. Productivity loss was estimated based on data from the Longitudinal integration database for health insurance and labour market studies at Statistics Sweden. Results: Patients with moderate to severe psoriasis had significantly lower HRQOL in EQ-5D than the general population (paper I). Women rated their HRQOL lower than men, even though men had more severe clinical skin involvement than women. (paper I). The generic measure EQ-5D and the dermatology-specific DLQI had moderate correlations whereas EQ-5D had low correlation with the clinical measure PASI (paper I). Patients who switched to a biologic agent during registration in PsoReg had significant improvements in all outcomes (paper II). Patients who fulfilled the criteria for moderate to severe psoriasis had the highest benefits of the biologic agents (paper II). The matched conventionally and biologically treated patients with moderate to severe psoriasis were essentially equal in important observable variables (paper III). The subgroup of patients not responding to conventional treatment had high potential benefits of biologic agents (paper III). Individuals with psoriasis had sick leave and disability pension to a larger extent than their matched controls (paper IV). Direct costs increased, whereas the indirect costs of productivity loss decreased between 2006 and 2009 (paper IV). Conclusion: Psoriasis is associated both with direct costs and indirect costs, and it has a negative impact on patients’ HRQOL. When evaluating psoriasis treatments and making decisions about treatment guidelines, both generic, dermatology-specific HRQOL measures, and clinical measures are necessary; as they answer to different needs. Although dependent on data quality, generalisability, and current pricing, results suggest that conventional treatments are suitable as first line and biologic agents as second line treatment. Results indicate that the different types of systemic treatments are not allocated optimally among patients with psoriasis in Swedish clinical practice.

Master of Agribusiness / Department of Agricultural Economics / Vincent R. Amanor-Boadu / It is estimated that the animal health biologics sector will increase by over 27% between 2015 and 2020. This projection and the increasing competition among the sector’s players suggests need to find ways to enhance their efficiencies in manufacturing to sustain their relative competitiveness. One approach to enhancing efficiencies is to ensure that all work is done once, i.e., everything is done right the first time. This research focused on human error as a major source of inefficiency in manufacturing and hypothesized that addressing issues that reduce human error would contribute to reducing inefficiencies. The research used the Kaizen process to assess the before and after counts of human error in a biologics manufacturing unit of Z Animal Health Company (ZAHC). The study found that human error accounted for about 51% of all sources of error in the pre-Kaizen period and only about 34% of all errors in the post-Kaizen period, a reduction in excess of 33.3%. Given that humans are directly or indirectly responsible for all activities in the manufacturing process, the Kaizen process also contributed to a reduction in most other error sources. For example, errors in raw materials and components went reduced by about 50%. We tested the hypothesis that undertaking the Kaizen was statistically effective in reducing human error compared to all other errors using a logit model. Our results confirmed this hypothesis, showing that the odds ratio of human error in the post-Kaizen period was about 50% of the odds of non-human error. The research suggests that in a highly technical manufacturing environment, such as in animal health biologics, human errors can be a major problem that can erode competitiveness quickly. Focusing employees’ on root causes of errors and helping them address these through structured quality-enhancing initiatives such as Kaizen produce superior results. It is, therefore, suggested that when organizations discover human error as a major source of inefficiency, it is prudent to help employees understand what they do and how what they do contributes to the overall performance of the organization. This appreciation of how their actions fit into the big picture could provide a foundation upon which significant improvements can be achieved.

Biologics such as DNA and protein have immense biomedical applications, especially in diagnosis and therapy. However, many barriers hinder these applications, including biologics transport and liability in biological systems. Therefore, biocompatible and stable nanocarriers with high Biologics loading efficiency can provide a platform for advances in biologics applications. Metal-organic frameworks (MOFs) have gained significant interest within the biomedical field, mainly because of their building block versatility, porosity, stability, and chemical and biological functionality. Currently, increasing research is dedicated to improving MOFs biocompatibility, stability, and functionality for drug delivery. Using biomolecules as organic linkers could improve biocompatibility, physiological condition stability, and biological functionality. The main goal of this dissertation is to investigate the applicability of biomolecule-based Metal-organic frameworks (BioMOFs) as nanocarriers to achieve cellular delivery of active biologics. Herein, we analyzed adenine and saccharate metal−organic frameworks (BioMOF) in terms of biocompatibility, loading capability, protection, and cellular delivery of biologics. Our findings suggest that the usage of biomolecules as an organic linker generates BioMOFs with reduced cytotoxicity compared with the widely used MOFs such as Zinc Imidazole framework-8 (ZIF-8). In addition, the base-pairing functionality of coordinated adenine of KAUST-BioMOFs (KBMs) is preserved and can be used to load ssDNA. Both KAUST-BioMOFs (KBMs) and Zinc adenineated framework (ZAF) load, protect, and deliver functional ssDNA to cells. In addition, we showed the possibility of in situ encapsulation of active lysozyme in zinc saccharate (Zn-Sac) with modified synthesis procedures.

No description available.

The two options for treatment of the inflammatory bowel disease Crohn’s Disease are surgery and pharmacotherapy. Pharmacotherapy with the goal of inducing and maintaining remission is the preferred treatment route, but the current medications are not entirely effective in achieving these goals. Approximately half of Crohn’s Disease patients will be required to have surgical bowel resection within 20 years of diagnosis, and many patients are at higher risk of adverse events such as cancer, either directly as a result of Crohn’s Disease or due to side-effects of the drugs used to treat the condition. Medical management of the disease is very complicated and there is a relative lack of uniformity in treatment. Different drugs used either in monotherapy, sequential therapy, or combination therapy produce differing levels of efficacy and different outcomes. This analysis provides an overview of the four major classes of drugs used in the treatment of Crohn’s Disease and a discussion of the overall efficacy of the different methods of treatment. While more studies need to be conducted into the differing outcomes of monotherapy, sequential therapy, and combination therapy, it appears as though any treatment involving the use of biologics such as tumor necrosis factor alpha (TNF-alpha) inhibitors results in improved outcomes relative to treatment styles that lack the use of biologics.

The purpose of this study was to investigate if the addition of biologic materials and/or oral steroids would affect horizontal bone gain, or the bone density of the grafted bone in horizontal alveolar ridge augmentations. A retrospective chart review was completed to assess the clinical and radiographic outcomes of 53 ridge augmentation patients. An average bone gain of 3.6mm of width was found in our study based on radiographic analysis. There were no statistically significant differences found in the linear bone gain with the addition of biologic materials and steroids. A marginally statistically significant difference was found in the bone density when biologics were added (p-value=0.0653). No statistically significant difference found in the bone density with the addition of oral steroids. The use of tenting screws and resorbable occlusive membranes and a combination of allograft and xenograft bone materials provides significant clinical and radiographic dimensional changes in alveolar ridge width.