Background

This project is an effort to understand how orders for IV immunoglobulin (IVIg) are documented and prescribed by physicians, and subsequently, how they are reviewed by insurance companies for the treatment of immune neuropathies.

Methods

A panel of neuromuscular specialists reviewed case records from 248 IVIg-naive patients whose in-home IVIg infusion treatment was submitted to insurance for authorization. After reviewing a case record, 1 panelist was asked to make a diagnosis and to answer several questions about the treatment. A second panelist reviewed the original record and follow-up records that were obtained for reauthorization of additional treatments and was asked to determine whether the patient had responded to the treatment.

Results

Our specialists believed that only 32.2% of 248 patients had an immune neuropathy and were appropriate candidates for IVIg therapy, whereas 46.4% had neuropathies that were not immune mediated. Only 15.3% of cases met electrodiagnostic criteria for a demyelinating neuropathy. Our specialists believed that 36.7% of 128 cases with follow-up records had responded to therapy. In cases in which the initial reviewer had predicted that there would be a response to IVIg, the second reviewer found that 54% had responded. This is compared with a 27% response rate when the first reviewer predicted that there would be no response (p = 0.019).

Conclusions

Our expert review finds that the diagnosis of immune neuropathies made by providers, and subsequently approved for IVIg therapy by payers, is incorrect in a large percentage of cases. If payers include an expert in their review process, it would improve patient selection, appropriate use, and continuation of treatment with this expensive therapeutic agent.

Duvoglustat HCl (AT2220, 1-deoxynojirimycin) is an investigational pharmacological chaperone for the treatment of acid α-glucosidase (GAA) deficiency, which leads to the lysosomal storage disorder Pompe disease, which is characterized by progressive accumulation of lysosomal glycogen primarily in heart and skeletal muscles. The current standard of care is enzyme replacement therapy with recombinant human GAA (alglucosidase alfa [AA], Genzyme). Based on preclinical data, oral co-administration of duvoglustat HCl with AA increases exposure of active levels in plasma and skeletal muscles, leading to greater substrate reduction in muscle. This phase 2a study consisted of an open-label, fixed-treatment sequence that evaluated the effect of single oral doses of 50 mg, 100 mg, 250 mg, or 600 mg duvoglustat HCl on the pharmacokinetics and tissue levels of intravenously infused AA (20 mg/kg) in Pompe patients. AA alone resulted in increases in total GAA activity and protein in plasma compared to baseline. Following co-administration with duvoglustat HCl, total GAA activity and protein in plasma were further increased 1.2- to 2.8-fold compared to AA alone in all 25 Pompe patients; importantly, muscle GAA activity was increased for all co-administration treatments from day 3 biopsy specimens. No duvoglustat-related adverse events or drug-related tolerability issues were identified.

The Covid-19 pandemic challenged health care delivery systems worldwide. Many acute care hospitals in communities that experienced surges in cases and hospitalizations had to make decisions such as rationing scarce resources. Hospitals serving low-income communities, communities of color, and those in other historically marginalized or vulnerable groups reported the greatest operational impacts of surges. However, cross-institutional collaborations within jurisdictions offer unique opportunities to prevent or mitigate health disparities in resource utilization and access to care. In January 2020, in response to the emerging coronavirus epidemic, the San Francisco Department of Public Health (SFDPH) and local hospital and health systems partners convened to align and coordinate medical surge planning and response. Adopting a governance structure of mutual accountability and transparency, the San Francisco Health Systems Collaborative guided local medical and public health response in the areas of medical surge, vaccination administration, testing, and therapeutics. Four principles guided the collaborative response: (1) shared priorities, (2) clear governance and accountability, (3) data transparency, and (4) operational coordination. High-level priorities established included protecting vulnerable people, protecting health care workers, and maintaining health system capacity. The governance structure consisted of three layers: local hospital and health systems CEOs coordinating with SFDPH executives; hospital chief medical and nursing officers coordinating high-level surge capacity assessments and mitigation plans; and local clinical operational managers working with public health response operational leaders to coordinate scarce resource utilization. Fluctuating with the tempo of the disease indicators and medical surge, governance and coordination were maintained through a tiered meeting and reporting system. Data visibility and transparency were key principles facilitating operational decision-making and executive-level coordination of resources, including identifying additional surge bed capacity for use systemwide, as well as ensuring efficient and equitable vaccine distribution through implementation of five mass-vaccination sites with prioritized access for vulnerable communities. Applying these four principles of shared priorities, accountability, transparency, and operational coordination and pragmatism helped the public health and individual hospital systems make contributions to the overall response that were aligned with their unique strengths and resources. Publication here represents the first official public use of the name San Francisco Health Systems Collaborative (which had served as the term used internally to refer to the group) and the first time codifying this structure. Through this coordination, San Francisco achieved one of the lowest Covid-19 death rates and had one of the highest vaccination and booster rates, compared with rates across California or the United States. Similar principles and implementation methods can be adopted by other health jurisdictions for future emergency outbreak response.