Thrombopoietin Receptor Agonists and Other Second-Line Therapies for Immune Thrombocytopenia: A Narrative Review With a Focus on Drug Access in Canada.

INTRODUCTION: Immune thrombocytopenia (ITP) is an autoimmune disease characterized by low platelet counts and increased risk of bleeding. After corticosteroids with or without intravenous immune globulin (first-line treatment), second-line treatment options include rituximab, splenectomy, thrombopoietin receptor agonists (TPO-RAs), and fostamatinib. In Canada, the choice of second-line therapy is influenced by access to medications. The goals of this narrative review are to 1) summarize the evidence for the use of TPO-RAs and other second-line therapies in ITP and 2) highlight differences in public funding criteria for TPO-RAs across provinces and territories in Canada. METHODS: We conducted a literature review of second-line therapies for ITP. We solicited information on public funding programs for TPO-RAs in Canada from health care providers, pharmacists, and provincial ministries of health. RESULTS: Head-to-head trials involving TPO-RAs, rituximab, splenectomy, and fostamatinib are lacking. There is substantial evidence of effect for TPO-RAs in improving platelet count levels, health-related quality of life, bleeding, and fatigue from placebo-controlled trials and observational studies; however, access to TPO-RAs through provincial funding programs in Canada is variable. Splenectomy failure is a prerequisite for the funding of TPO-RAs in Ontario, Manitoba, and Saskatchewan, but not in Alberta or Quebec. Other provinces either do not have access to public funding or funding is provided on a case-by-case basis. DISCUSSION: TPO-RAs are effective second-line therapies for the treatment of ITP; however, access is variable across Canada, which results in health disparities and poor uptake of international treatment guidelines.

Frontline Treatment of the Young, Fit Patient with CLL: A Canadian Perspective.

From a Canadian perspective, there has been a limited discussion on the frontline management of young, fit patients with chronic lymphocytic leukemia (CLL). The prevalence of this population ranges between 2 and 22 per 100,000 persons in Canada and varies by region. Until recently, fixed-duration fludarabine-based chemoimmunotherapy (CIT) was the primary treatment option in Canada for this patient population. The ECOG1912 trial has since demonstrated that ibrutinib and rituximab therapy are as effective as fludarabine-cyclophosphamide-rituximab (FCR) in this population. The ALLIANCE trial showed that rituximab added no incremental benefit to ibrutinib. Canadian payors and physicians adopted ibrutinib monotherapy as the CLL standard of care, even in the young, fit population, although frontline ibrutinib therapy is often reimbursed by provincial public drug plans only in patients with high-risk disease or those who are unfit to receive fludarabine. Young, fit patients with CLL and their physicians may now choose between continuous ibrutinib monotherapy and fixed-duration CIT with FCR. Factors affecting this choice include patient preference and the short- and long-term toxicity profiles of both regimens, and a risk-based algorithm is provided. As new continuous-therapy options enter the market, all treatment choices present benefits and risks that must be communicated to the patient.

Immunization Recommendations for Pediatric Patients with Chronic Kidney Disease, Nephrotic Syndrome, and Renal Transplants: A Literature Review and Quality Improvement Project.

Pediatric patients with chronic kidney disease (CKD) have an increased risk of developing vaccine-preventable diseases due to reduced immunization coverage. Studies have demonstrated that reduced immunization coverage in this population is related to barriers, such as frequent hospitalization, lack of knowledge, and concerns about safety and efficacy. This article examines a nurse practitioner-led quality improvement project (QIP) conducted in an outpatient pediatric nephrology clinic. The QIP focused on educating pediatric providers related to age-appropriate immunizations for children with CKD or nephrotic syndrome, and those who are renal transplant candidates and recipients. A process is now in place to review immunization records upon initial visit and annually, and to notify primary care providers of current recommendations for this population.

Effectiveness of an Anger Intervention for Military Members with PTSD: A Clinical Case Series.

OBJECTIVE: Problematic anger is a significant clinical issue in military personnel, and is further complicated by comorbid post-traumatic stress disorder (PTSD). Despite increasing numbers of military personnel returning from deployment with anger and aggression difficulties, the treatment of problematic anger has received scant attention. There are currently no interventions that directly target problematic anger in the context of military-related PTSD. The aim of this case series is to examine the effectiveness of an intervention specifically developed for treating problematic anger in current serving military personnel with comorbid PTSD. METHODS: Eight Australian Defence Force Army personnel with problematic anger and comorbid PTSD received a manualized 12-session cognitive behaviorally based anger intervention, delivered one-to-one by Australian Defence Force mental health clinicians. Standardized measures of anger, PTSD, depression, and anxiety were administered pre- and post-treatment. RESULTS: The initial mean severity scores for anger indicated a high degree of pre-treatment problematic anger. Anger scores reduced significantly from pre to post-treatment (d = 1.56), with 88% of participants exhibiting meaningful reduction in anger scores. PTSD symptoms also reduced significantly (d = 0.96), with 63% of participants experiencing a clinically meaningful reduction in PTSD scores. All of those who took part in the therapy completed all therapy sessions. CONCLUSIONS: This brief report provides preliminary evidence that an intervention for problematic anger not only significantly reduces anger levels in military personnel, but can also significantly reduce PTSD symptoms. Given that anger can interfere with PTSD treatment outcomes, prioritizing anger treatment may improve the effectiveness of PTSD interventions.