BackgroundAsthma, one of the most common chronic respiratory diseases, affects about 3 million Canadians. The objective of this study is to provide a comprehensive evaluation of the published literature that reports on the clinical, economic, and humanistic burden of asthma in Canada.MethodsA search of the PubMed, EMBASE, and EMCare databases was conducted to identify original research published between 2000 and 2011 on the burden of asthma in Canada. Controlled vocabulary with “asthma” as the main search concept was used. Searches were limited to articles written in English, involving human subjects and restricted to Canada. Articles were selected for inclusion based on predefined criteria like appropriate study design, disease state, and outcome measures. Key data elements, including year and type of research, number of study subjects, characteristics of study population, outcomes evaluated, results, and overall conclusions of the study, were abstracted and tabulated.ResultsThirty-three of the 570 articles identified by the clinical and economic burden literature searches and 14 of the 309 articles identified by the humanistic burden literature searches met the requirements for inclusion in this review. The included studies highlighted the significant clinical burden of asthma and show high rates of healthcare resource utilization among asthma patients (hospitalizations, ED, physician visits, and prescription medication use). The economic burden is also high, with direct costs ranging from an average annual cost of $366 to $647 per patient and a total annual population-level cost ranging from ~ $46 million in British Columbia to ~ $141 million in Ontario. Indirect costs due to time loss from work, productivity loss, and functional impairment increase the overall burden. Although there is limited research on the humanistic burden of asthma, studies show a high (31%-50%) prevalence of psychological distress and diminished QoL among asthma patients relative to subjects without asthma.ConclusionsAs new therapies for asthma become available, economic evaluations and assessment of clinical and humanistic burden will become increasingly important. This report provides a comprehensive resource for health technology assessment that will assist decision making on asthma treatment selection and management guidelines in Canada.

To describe the characteristics of patients receiving belimumab, overall patterns of systemic lupus erythematosus (SLE) care, clinical outcomes, and changes in glucocorticoid dose following 6 months of therapy with belimumab, and healthcare resource utilization in belimumab users in Canadian clinical practice settings. Retrospective multicenter medical chart review study of adult patients with SLE who were prescribed belimumab as part of usual care and who received ≥8 infusions or 6 months of treatment. Primary endpoints included physician-determined overall clinical improvement from baseline, glucocorticoid use, and physician-determined SLE disease severity at Month 6. In total, 52 patients were included in the study. At belimumab initiation, 5.8/76.9/17.3% of patients had mild/moderate/severe SLE, respectively. Oral glucocorticoids were discontinued in 11.4% of patients and 59.1% received a lower dose at Month 6. At Month 6, 80.8/57.7/17.3% of patients had a physician-determined clinical improvement of ≥20/≥50/≥80%, respectively. Sixteen patients had a SLE Disease Activity Index-2K score at both baseline and Month 6, with a mean improvement of 2.6 ± 5.3 from 8.1 ± 3.2 at baseline. No formal disease assessment tool was utilized for 42.3% of study patients at baseline. This study provides the first real-world insights into belimumab use in Canada. It demonstrates significant reduction or discontinuation of glucocorticoid dose in 70.5% of patients and clinically significant improvement following 6 months’ belimumab therapy. The high number of patients with no formal disease activity assessments highlights a key care gap in SLE treatment in the real-world setting.

Introduction: Benign prostatic hyperplasia (BPH) is common in men 50 years old and older. The main treatment options are alpha-blockers (such as tamsulosin), which reduce symptoms, and 5-alpha reductase inhibitors (such as dutasteride), which reduce symptoms and slow disease progression. Clinical studies have demonstrated that dutasteride-tamsulosin combination therapy is more effective than either monotherapy to treat symptomatic BPH. We studied the cost-effectiveness in Canada of the dutasteride (0.5 mg/day) and tamsulosin (0.4 mg/day) combination compared with tamsulosin or dutasteride monotherapy. Methods: A Markov model was developed which follows a cohort of male BPH patients ≥50 with moderate to severe lower urinary tract symptoms (LUTS). The model estimates costs to the Canadian health care system and outcomes (in terms of quality adjusted life years [QALYs]) at 10 years and over a patient's lifetime. The dutasteride-tamsulosin combination was compared to each of tam-sulosin monotherapy and dutasteride monotherapy. Results: Compared with tamsulosin, the combination was more costly and produced better patient outcomes. Over a lifetime, the incremental cost-effectiveness ratio was CAN$25 437 per QALY gained. At a willingness to pay CAN$50 000 per QALY, the probability of combination therapy being cost-effective was 99.6%. Compared with dutasteride, the combination therapy was the dominant option from year 2, offering improved patient outcomes at lower cost. The probability that combination therapy is more cost-effective than dutasteride was 99.8%. Conclusion: Combination therapy offers important clinical benefits for patients with symptomatic BPH, and there is a high probability that it is cost-effective in the Canadian health care system relative to either monotherapy.

Objective To examine the role of disease activity on organ damage over 5 years in patients with active systemic lupus erythematosus (SLE) despite standard of care. Methods This analysis of the University of Toronto Lupus Clinic cohort assessed organ damage (measured by Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index [SDI]) in patients with active SLE (SLE Disease Activity Index- 2000 [SLEDAI-2K] ≥6), using Cox proportional time-independent hazard models. Subgroup analyses were conducted in patients with SLEDAI-2K 6 or 7, 8 or 9, and ≥10 at baseline, and in the overall study population by steroid dose at study entry (<7.5 vs ≥7.5 mg/day). Results Among the overall study population (N=649), SDI progression was observed in 209 (32.2%) patients over the 5-year follow-up. Mean SDI change in patients with a score >0 was generally consistent across all SLEDAI-2K subgroups. Multivariable analyses identified age at study start (hazard ratio [HR] 1.03, p<0.0001), steroid dose (HR 2.03, p<0.0001), immunosuppressants (HR 1.44, p=0.021), and SLEDAI-2K (subgroup analyses HR 1.64─2.03, p=0.0017─<0.0001) as the greatest risk factors for SDI progression, while a study start date after the year 2000 had a protective effect on SDI progression compared with a start date prior to the year 2000 (HR 0.65, p=0.0004). Conclusion Patients within the higher SLEDAI-2K subgroups at study entry, or receiving high doses of steroids, were more likely to have organ damage progression.

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Higher SLEDAI-2K at study entry was the single major independent predictor of higher SLEDAI-2K over time, reflecting frequent persistence of active disease, even in patients with longstanding disease. This highlights gaps in the optimal treatment of SLE.

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Purpose: To develop and characterize low-surfactant microemulsion (ME) gels to enhance topical delivery of poorly soluble drugs. Method: Five low surfactant ME formulations were manufactured following the construction of pseudo-ternary phase diagrams. The MEs were screened for their ability to dissolve a poorly soluble new chemical entity (Model Drug X). Various viscosity imparting agents like Carbopol 934, Colloidal Silica, HPMC K100M, Lubrajel NP, and Xanthan Gum were evaluated for the manufacture of these ME gels. Each ME gel was then further evaluated for physical stability, including assessing rheological profiles. In vitro release profiles were also determined and compared to a conventional ointment. Results: Three of the five low surfactant MEs developed (ME1, ME4 and ME5) were capable of dissolving Model Drug X up to 14 fold higher than the conventional ointment formulation. ME1 and ME4 gels comprising Xanthan gum or Carbopol 934 were physically stable, while ME5 gel was stable only with Colloidal Silica. The ME5 gel with Colloidal Silica showed an irreversible increase in its elastic modulus when exposed to high temperature, indicating that the formulation would be less suitable for commercial use. The Xanthan Gum and Colloidal Silica gels yielded significantly higher release rates (8 - 10 fold) compared to a conventional ointment and formulations containing Carbopol 934. The significant difference in drug release rates between Xanthan Gum and Carbopol 934 indicated that choice of viscosity imparting agent played an important role in governing drug release from ME gels. Conclusion: ME gels were developed with low surfactant concentrations and improved formulation characteristics, which increased the solubility and subsequent release of a poorly soluble drug. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.