In-depth interviews of patients with primary immunodeficiency who have experienced pump and rapid push subcutaneous infusions of immunoglobulins reveal new insights on their preference and expectations

Grégoire Jacques Noël Cozon,1 Pierre Clerson,2 Annaïk Dokhan,3 Yann Fardini,2 Taylor Pindi Sala,4 Jean-Charles Crave4 1Department of Clinical Immunology and Rheumatology, Edouard Herriot Hospital, Lyon, France; 2Soladis Clinical Studies, Roubaix, France; 3KPL, Paris, France; 4Octapharma France, Boulogne, France Purpose: Patients with primary immunodeficiency (PID) often receive immunoglobulin replacement therapy (IgRT). Physicians and patients have the choice between various methods of administration. For subcutaneous immunoglobulin infusions, patients may use an automated pump (P) or push the plunger of a syringe (rapid push [RP]). P infusions are performed once a week and last around 1 hour. RP decreases the duration of administration, but requires more frequent infusions.Patients and methods: Eight out of 30 patients (coming from a single center) who had participated in the cross-over, randomized, open-label trial comparing P and RP participated in a focus group or underwent in-depth interviews. Patients had a long history of home-based subcutaneous immunoglobulin using P. The trial suggested that RP had slightly greater interference on daily life than P, but similar efficacy and better cost-effectiveness. When asked about the delivery method they had preferred, around one-third of patients pointed out RP rather than P. In-depth interviews may reveal unforeseen reasons for patients’ preferences. Results: Interviews underlined the complexity of the relationship that the patients maintain with their disease and IgRT. Even if they recognized the genetic nature of the disease and claimed PID was a part of them, patients tried not to be overwhelmed by the disease. IgRT by P was well integrated in patients’ routine. By contrast, RP too frequently reminded the patients of their disease. In addition, some patients pointed out the difficulty of pushing the plunger due to the viscosity of the product. Coming back too frequently, RP was not perceived as time saving over a week. Long-lasting use of P could partly explain patients’ reasonable reluctance to change to RP.Conclusion: In-depth interviews of PID patients highlighted unforeseen reasons for patients’ preference that the physician needs to explore during the shared medical decision-making process. Keywords: in-depth interviews, primary immunodeficiency, patients’ expectations, preference, immunoglobulins, immunoglobulins replacement therapy, pump, rapid push, syring

In utero exposure to Azathioprine in autoimmune disease. Where do we stand?

Azathioprine (AZA), an oral immunosuppressant, is safe during pregnancy. Some reports suggested different impairments in the offspring of mothers with autoimmune diseases (AI) exposed in utero to AZA. These observations are available from retrospective studies or case reports. However, data with respect to the long-term safety in the antenatally exposed child are still lacking. The aim of this study is to summarize the current knowledge in this field and to focus on the need for a prospective study on this population. We performed a PubMed search using several search terms. The actual data show that although the risk of congenital anomalies in offspring, as well as the infertility risk, are similar to those found in general population, there is a higher incidence of prematurity, of lower weight at birth and an intra-uterine delay of development. There is also an increased risk of materno- fetal infections, especially cytomegalovirus infection. Some authors raise the interrogations about neurocognitive impairment. Even though the adverse outcomes might well be a consequence of maternal illness and disease activity, interest has been raised about a contribution of this drug. However, the interferences between the external agent (in utero exposure to AZA), with the host (child genetic susceptibility, immune system anomalies, emotional status), environment (public health, social context, availability of health care), economic, social, and behavioral conditions, cultural patterns, are complex and represent confounding factors. In conclusion, it is necessary to perform studies on the medium and long-term outcome of children born by mothers with autoimmune diseases, treated with AZA, in order to show the safety of AZA exposure. Only large-scale population studies with long-term follow-up will allow to formally conclude in this field. Take home messages: • There is no study on a significant number of subjects concerning the medium and long-term outcome of children born by mothers with autoimmune disease treated with AZA. • As AZA use is related to underlying disease and disease activity and many confounders interfere with AZA treatment, there is a major difficulty to distinguish between the influence of the disease itself on the risk of adverse birth outcome and potential AZA effects in offspring at medium and long term. • Data need to be implemented with large, multicenter studies