[Assessment of immunoglobulins in a long-term non-interventional study (SIGNS Study). Rationale, design, and methods].

Non-modified human immunoglobulins (IgG) are standard of care for replacement therapy with primary (inherited) immunodeficiencies, and secondary immunodeficiencies due to multiple myeloma (MM) or chronic lymphocytic leukemia (CLL). Further, they have effectively been used as immunomodulation in neurological autoimmune diseases such as Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), and multifocal motor neuropathy (MMN). A variety of IgG preparations for intravenous and subcutaneous use are available. In view of the broad range of indications, data on the utilization of the IgG preparations in everyday clinical care are of high clinical interest. Furthermore, data on the outcomes of IgG therapy outside the setting of controlled clinical trials are needed. Therefore, the SIGNS study (Assessment of Immunoglobulins in a Long-Term Non-Interventional Study) was set up as a non-interventional prospective open-label cohort study and was approved by the ethics committee. Led by an interdisciplinary steering board, hospital- and office-based investigators in 30-40 centers throughout Germany (neurologists, pediatricians, oncologists, other) will document approximately 300 patients, and will follow them for at least 2 years. Patients of both genders and any age are eligible if they have received, or are scheduled for, IgG therapy for primary or severe secondary immunodeficiency or neurological autoimmune diseases, and have provided written informed consent. No exclusion criteria have been defined in order to minimize selection bias. Long-term outcome data will be collected on patient characteristics in the various indications, drug utilization (e.g., treatment and dosing patterns), effectiveness (i.e., number of infections), tolerability, health-related quality of life, and economic variables (number of hospitalizations, sick-leave days, etc.) with the possibility to estimate direct costs. For the neurological autoimmune diseases, detailed data will be gathered, among others, on neurological function, muscular function, physical function (grip strength, INCAT disability scale, etc.) and stabilization or progression of symptoms over time. Data collection in SIGNS is performed using a secure internet site and an MySQL database. A number of quality measures are routinely performed including automated plausibility checks at data entry, queries, and on-site monitoring with source data verification. It is expected that SIGNS will contribute to optimization of therapy in this diverse patient population.