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Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs.
Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel.
Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1–25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0–88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE- syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%—subcutaneous; 29%—intravenous; 1%—unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy.
Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment.
Objective: Biologics have an important role in the treatment of juvenile idiopathic arthritis (JIA). Long‐term safety data are limited. Direct comparison of different agents regarding occurrence of adverse events (AEs), especially of rare events, requires large quantities of patient years. In this analysis, long‐term safety with regard to AE of special interest (AESI) was compared between different biologics.
Methods: Patients with nonsystemic JIA were selected from the German BIKER registry. Safety assessments were based on AE reports. Number of AEs, serious AEs, and 25 predefined AESIs, including medically important infection, uveitis, inflammatory bowel disease, cytopenia, hepatic events, anaphylaxis, depression, pregnancy, malignancy, and death, were analyzed. Event rates and relative risks were calculated using AEs reported after first dose through 70 days after last dose.
Results: A total of 3873 patients entered the analysis with 7467 years of exposure to biologics. The most common AESIs were uveitis (n = 231) and medically important infections (n = 101). Cytopenia and elevation of transaminases were more frequent with tocilizumab (risk ratio [RR] 8.0, 95% confidence interval [CI] 4.2‐15, and RR 4.7, 95% CI 1.8‐12.2, respectively). Anaphylactic events were associated with intravenous route of administration. In patients ever exposed to biologics, eight malignancies were reported. Six pregnancies have been documented in patients with tumor necrosis factor inhibitors. No death occurred in this patient cohort during observation.
Conclusion: Surveillance of pharmacotherapy as provided by the BIKER registry is an import approach, especially for long‐term treatment of children. Overall, tolerance was acceptable. Differences between biologics were noted and should be considered in daily patient care.
COPA syndrome is a newly discovered hereditary immunodeficiency affecting the lung, kidneys, and joints. The mutated gene encodes the α subunit of the coatomer complex I, a protein transporter from the Golgi back to the endoplasmic reticulum. The impaired return of proteins leads to intracellular stress. The syndrome is an autoimmune and autoinflammatory disease that can be grouped among the interferonopathies. The knowledge about COPA syndrome and its treatment is still limited. In this paper, we describe an additional patient, a 15-year-old girl with rheumatoid factor-positive polyarthritis and rheumatoid nodules since the age of 2, who developed interstitial lung disease. The detected mutation c.698G>A was causing the disease. The patient presented with symmetric polyarthritis on wrists, fingers, and hip and ankle joints, with significant functional impairment, and high disease activity. Laboratory parameters demonstrated chronic inflammation, hypergammaglobulinemia, high titre ANA (antinuclear antibodies) and CCP (anti-citrullinated protein) antibodies, and rheumatoid factors. Therapies with various DMARDs (Disease Modifying Anti-Rheumatic Drugs) and biologicals failed. Upon baricitinib application, the clinical activity decreased dramatically with disappearance of joint pain and morning stiffness and significant decrease of joint swelling. A low disease activity was reached after 12 months, with complete disappearance of rheumatoid nodules. In contrast to IL-1 (interleukin-1), IL-6, and TNF (tumor necrosis factor) inhibitors, baricitinib was very successful, probably because baricitinib acts as a JAK-1/2 (janus kinase-1/2) inhibitor in the IFNα/β (inteferone α/β) pathway. A relatively higher dose in children is necessary. COPA syndrome represents a novel disorder of intracellular transport. Reviewing published literature on COPA syndrome, in addition to our patient, there were 31 cases further described.