Immunoglobulin Replacement Therapy Research Articles

P256 Managing a patient with multiple reactions to immunoglobulin replacement therapy

Systemic adverse events are more common with intravenous compared to subcutaneous immunoglobulin administration. However, systemic reactions can occur with subcutaneous products as well. When a patient reacts to both types of products it can significantly limit a patient’s treatment options.

Selecting haematological malignancy patients for intravenous immunoglobulin.

Prior randomised studies of immunoglobulin replacement therapy have studied mixed populations with or without a history of infections. Immunoglobulin therapy is expensive and in limited supply suggesting that optimising patient selection is of value. In this retrospective study, infection history identified high-risk groups benefiting from treatment. A group of patients without any infection history had a low risk of infection without immunoglobulin.

Treatment with Hizentra in patients with primary and secondary immunodeficiencies: a real-life, non-interventional trial

BackgroundAlthough Hizentra is indicated for immunoglobulin replacement therapy in patients with primary and secondary immunodeficiencies, phase III trials have focused on patients with primary immunodeficiencies. In this 9-month, real-life, prospective, non-interventional, longitudinal, multicenter study of patients with primary and secondary immunodeficiencies in France, treatment modalities (primary endpoint), efficacy, safety, tolerability, quality of life, and treatment satisfaction were evaluated using descriptive statistics.ResultsStarting in January 2012, 117 patients were enrolled (99 adults, 18 children). Secondary immunodeficiencies were present in 48.7 % of patients. At follow-up, injections were administered every 7 days in 92.2 % of patients. Nine patients (7.8 %) were taking Hizentra every 10–14 days. The median dose of Hizentra administered was 0.1 g/kg/injection. Fifty-six patients were administered doses <0.1 g/kg/injection and 13 patients were administered doses >0.2 g/kg/injection. Mean trough IgG titers were 9.0 ± 3.3 g/L (median 8.3 g/L). The mean yearly rate of infection was 1.2 ± 1.9. Mean scores on the Short Form-36 physical and mental component summaries were 46.3 ± 10.0 and 46.6 ± 9.3, respectively. Scores on the Treatment Satisfaction Questionnaire for Medication ranged from 69.9 ± 19.9 to 88.3 ± 21.2 depending on the domain. Treatment with Hizentra was well tolerated. No single drug-related systemic reaction occurred in more than one patient and few local reactions were reported (n = 5).ConclusionsUnder real-life conditions and in a cohort that included patients with primary and secondary immunodeficiencies, treatment with Hizentra was effective and well tolerated and patients were generally satisfied with the treatment.

The use of Immunoglobulin Therapy in Primary Immunodeficiency Diseases.

Immunoglobulin therapy represents a lifesaving intervention for many patients with primary immunodeficiency (PID). Antibody defects represent approximately half of the well-known PIDs requiring immunoglobulin replacement therapy. Following immunoglobulin therapy in PID patients, protection against serious upper and lower respiratory tract infections and pulmonary function improves which leads to an increase in the quality of life of these patients. Successful treatment of PID patients depends on the type of immunodeficiency, regular monitoring of the patient, comorbidities of the patient, and the availability of the products.

Post-polio syndrome in Algeria epidemiological profile and risk factors

The post-polio syndrome (PPS), clinical entity that occurs at least 15 years of stability after acute polio results in specific symptoms. If its pathophysiology remains unsolved its functional impact is considerable. The objectives are two folds, establish the epidemiological profile and search the harmful elements for its prevention. Prospective descriptive study, from 2010 to 2013, about 104 former polio victims. The tools: pain-scale, fatigue-scale of Borg and a preset plug for data collection, including historical elements of polio and diagnostic criteria of Halstead. The analysis was done on SPSS. The prevalence of PPS is 46%. The average age of patients-SPP is 41.4 years. This syndrome is due to fatigue, muscle pain and/or joint, new muscle weakness in healthy or those already affected muscles, and intolerance to cold. The occurrences of risk factors for post polio syndrome are obesity (BMI ≥ 30 kg/m 2 ) and age over 4 years in the acute phase of polio. In our study, the prevalence of PPS is 46%, a result close to a Swedish study but different from that reported by a French study (23%). The average age is 40 years, whereas it is more advanced in the other series. Age AAP achieving average is between 1 to 3 years with a frequency of 68.75%, results similar to those of the Norwegian team. Sex is not a risk factor for PPS, is it a selection bias? Muscle pain is 60.42% consistent with other studies. The fatigue, main symptom joining results of Australian and American teams. New amyotrophies and constant sign are found in all series. The cold intolerance is more pronounced in our study appears in other series: – PPS syndrome is at the origin of a degradation of the quality of life; – Prevention is to fight against risk factors, especially obesity. The management of SPP is long with a multidisciplinary collaboration. Therapeutic weapons ranging from economics of daily activity to the immunoglobulin replacement therapy.

Epidermodysplasia verruciformis as a manifestation of ARTEMIS deficiency in a young adult

Abstract This study is the first to report epidermodysplasia verruciformis (EV) associated with ARTEMIS deficiency in a young adult. This broadens the clinical scope of ARTEMIS deficiency, and provides a new genetic etiology for susceptibility to EV.

Immunoglobulin replacement therapy reduces chronic rhinosinusitis in patients with antibody deficiency.

Patients with primary antibody deficiencies have an increased frequency of sinonasal and pulmonary infections. Immunoglobulin (Ig) replacement is a standard therapy for common variable immunodeficiency (CVID) and other antibody deficiency diseases. Although there is convincing evidence that Ig replacement reduces pulmonary infections, there is little evidence that it reduces sinus infections or abates chronic rhinosinusitis (CRS). This study aims to identify the impact of Ig replacement on CRS in antibody deficiencies. A single-center, retrospective chart review of adult patients from 1995 to 2015 was performed. Inclusion criteria were diagnosis of CVID or specific antibody deficiency (SAD), history of CRS requiring medical and/or surgical management within the year prior to presentation, treatment with Ig replacement therapy, and follow-up interval of at least 1 year after initiating Ig replacement. Patients with secondary immune deficiencies were excluded. Thirty-one patients met criteria. Data collected included pretreatment and posttreatment Lund-Mackay scores, and frequency of sinusitis and pulmonary infections requiring rescue antibiotics. Statistical analysis was performed using Wilcoxon signed-rank tests. A significant decline in the Lund-Mackay score was evidenced from pretreatment to posttreatment (p < 0.01). Treatment also resulted in significantly lower rates of sinusitis (p < 0.01) and pulmonary infections (p < 0.01). Additionally, 56% of patients who were on prophylactic antibiotics prior to Ig replacement were able to discontinue their use. We present objective evidence showing that Ig replacement therapy has a positive impact on the frequency of sinusitis and confirm its positive impact on pulmonary infections in adult patients with CVID and SAD.

Prophylactic immunoglobulin therapy in secondary immune deficiency – an expert opinion

ABSTRACTIntroduction: In primary immunodeficiency (PID), immunoglobulin replacement therapy (IgRT) for infection prevention is well-established and supported by a wealth of clinical data. On the contrary, very little evidence-based data is available on the challenges surrounding the use of IgRT in secondary immune deficiencies (SID), and most published guidelines are mere extrapolations from the experience in PID.Areas covered: In this article, four European experts provide their consolidated opinion on open questions surrounding the prophylactic use of IgRT in SID, based on their clinical experience. The main topics are IgRT initiation, route of administration, dose optimization, and therapy discontinuation. The authors hope this discussion will be of assistance to practicing physicians in their daily decision-making.Expert commentary: Although growing experience indicates that IgRT could play an important role in the management of SID, very little robust evidence is available to guide clinical practice. The authors stress the urgent need for new studies in the field and discuss points they find of importance to design them adequately.

Subcutaneous Immunoglobulin Therapy for Hypogammaglobulinemia Secondary to Malignancy or Related Drug Therapy.

Immunoglobulin replacement therapy (IRT) has an important role in minimizing infections and improving the health-related quality of life (HRQoL) in patients with immunodeficiency, who would otherwise experience recurrent infections. These plasma-derived products are available as intravenous immunoglobulin (IVIg) or subcutaneous immunoglobulin (SCIg). The global demand for these products is growing rapidly and has placed pressure on supply. Some malignancies and their treatment (as well as other medical therapies) can lead to secondary hypogammaglobulinemia or secondary immunodeficiency (SID) requiring IRT. Although IVIg use in this cohort has well-established therapeutic benefits, little is known about SCIg use. A literature search in July 2015 found only 7 published articles on SCIg use. These articles found that both IRT modes had equivalent efficacy in regard to reduction of bacterial infections. In addition, SCIg was reported to produce higher serum IgG trough levels compared with IVIg on equivalent dosage with the added benefit of fewer adverse effects. Patient HRQoL reports demonstrate preference for SCIg because of reduced adverse effects and hospital visits. There are no health economic models published on SCIg use in SID, but models on primary immunodeficiency disease and IRT conclude that SCIg provided greater economic benefits than IVIg. The findings of this small number of reports suggest that SCIg therapy for patients with SID is likely to be beneficial for both the patient and health care providers. To substantiate wider use of SCIg in SID, larger and more detailed studies are needed to accurately quantify the effectiveness of SCIg.

Comprehensive activities to increase recognition of primary immunodeficiency and access to immunoglobulin replacement therapy in Poland.

The study presents an overview on current situation of primary immunodeficiency (PID) patients in Poland and the 2014 annual report of the Polish Working Group for Immunodeficiency (PWGID). The group was set up in 2005 to improve diagnosis, treatment, and care of patients with immunodeficiencies and currently includes 15 pediatric and 13 adult centers. According to PWGID report 4099, PID patients are recognized in Poland, with the prevalence 10.6/100,000. The majority of them (54.2%) have predominantly antibody deficiency (PAD). In 2014 alone, a total number of 731 newly diagnosed individuals are reported. As predicted, the vast majority (70%) of them have PAD. Approximately one third of PAD patients require immunoglobulin replacement therapy. Within the entire cohort, an intravenous route of immunoglobulin therapy dominates (67.3%). However, within the age groups, distribution of immunoglobulin therapy varies and seems to be age related. Among children, 36% receive subcutaneous immunoglobulin, while with adults 26%. Analysis of numbers of either newly recognized or treated patients indicates its dynamic increase in recent years. This is the result of comprehensive activities by PWGID supported by governmental institutions, outstanding foundations, and patient's organization. • Immunoglobulins' treatment has substantially changed the life of individuals with PAD. Patients with common variable immunodeficiency (CVID) or X-linked agammaglobulinemia (XLA) can live and lead a near normal life. Early diagnosis of the disease followed by earlier implementation of appropriate treatment, including gammaglobulin replacement therapy, improves the quality of life. • Targeted efforts of health care professionals and government are required to optimize diagnostic and therapeutic approach for PAD. What is New: • Comprehensive activities of PWGID lead to better recognition of PID individuals and should improve reporting Polish PIDs to the ESID database. • Following the joint efforts of immunologists, patient's, and governmental organizations in the end of 2014, the Therapeutic Program for Treatment Adults with PID was introduced, leading to universal access to currently available treatment options and to improve the quality of life.

Primary immunodeficiency and recalcitrant chronic sinusitis: a systematic review.

A subset of patients with chronic rhinosinusitis (CRS) has disease refractory to standard therapies. Primary immunodeficiency should be considered in this group. Past literature has demonstrated an association between immunodeficiency and chronic sinusitis. A systematic literature search was performed using OVID, MEDLINE, EMBASE, and Cochrane databases to identify English language papers containing original human data on subjects with primary immunodeficiency and chronic sinusitis. A total of 39 studies met inclusion criteria. Data was collected pertaining to immune dysfunction in patients with chronic sinusitis, the clinical workup for these patients, and the effectiveness of medical and surgical treatments. The studies were assessed to determine their level of evidence. The majority of studies were supported by Level 4 evidence. Up to 50% of patients with recalcitrant CRS were found to have immune dysfunction. The most frequent primary immunodeficiencies studied were common variable immunodeficiency (CVID) and X-linked agammaglobulinemia (XLA). Common collected data included measurement of serum immunoglobulins and functional antibody responses. Treatments reviewed include immunoglobulin replacement, long-term antibiotics and endoscopic sinus surgery. Patients with recalcitrant CRS should be evaluated for primary immunodeficiency. This should include as assessment of quantitative serum immunoglobulin levels as well as functional antibody responses. Medical therapy, particularly immunoglobulin replacement therapy, appears to be most effective when administered at high doses early in the disease course. The addition of surgery is less clearly supported, but may also provide benefit if performed early.

Clinical and immunologic phenotype associated with activated phosphoinositide 3-kinase δ syndrome 2: A cohort study

Activated phosphoinositide 3-kinase δ syndrome (APDS) 2 (p110δ-activating mutations causing senescent Tcells, lymphadenopathy, and immunodeficiency [PASLI]-R1), a recently described primary immunodeficiency, results from autosomal dominant mutations in PIK3R1, the gene encoding the regulatory subunit (p85α, p55α, and p50α) of class IA phosphoinositide 3-kinases. We sought to review the clinical, immunologic, and histopathologic phenotypes of APDS2 in a genetically defined international patient cohort. The medical and biological records of 36 patients with genetically diagnosed APDS2 were collected and reviewed. Mutations within splice acceptor and donor sites of exon 11 of the PIK3R1 gene lead to APDS2. Recurrent upper respiratory tract infections (100%), pneumonitis (71%), and chronic lymphoproliferation (89%, including adenopathy [75%], splenomegaly [43%], and upper respiratory tract lymphoid hyperplasia [48%]) were the most common features. Growth retardation was frequently noticed (45%). Other complications were mild neurodevelopmental delay (31%); malignant diseases (28%), most of them being B-cell lymphomas; autoimmunity (17%); bronchiectasis (18%); and chronic diarrhea (24%). Decreased serum IgA and IgG levels (87%), increased IgM levels (58%), B-cell lymphopenia (88%) associated with an increased frequency of transitional Bcells (93%), and decreased numbers of naive CD4 and naive CD8 cells but increased numbers of CD8 effector/memory Tcells were predominant immunologic features. The majority of patients (89%) received immunoglobulin replacement; 3 patients were treated with rituximab, and 6 were treated with rapamycin initiated after diagnosis of APDS2. Five patients died from APDS2-related complications. APDS2 is a combined immunodeficiency with a variable clinical phenotype. Complications are frequent, suchassevere bacterial and viral infections, lymphoproliferation, and lymphoma similar to APDS1/PASLI-CD. Immunoglobulin replacement therapy, rapamycin, and, likely in the near future, selective phosphoinositide 3-kinase δ inhibitors are possible treatment options.

Dermo-hypodermite bactérienne « à bascule » chez un patient atteint d’hypogammaglobulinémie liée à l’X

In cases of immunodeficiency, a systemic infection may be revealed by atypical symptoms, particularly those involving the skin. The present case describes a 19-year-old male with X-linked hypogammaglobulinemia, or Bruton agammaglobulinemia, treated with intravenous immunoglobulin G antibodies. Over a 6-week period, the patient developed recurrent plaques in both legs, first on one and then on the other, without fever. Blood cultures were repeated and the fifth pair proved positive for Campylobacter jejuni. An abdominal scan showed appendicitis without intestinal signs. The patient was treated with azithromycin for 2 weeks, which resulted in full recovery from the skin lesions. Campylobacter bacteremia infections are severe and carry a 15% mortality rate at 30 days. The majority of affected patients present humoral immunodeficiency. The literature contains reports of 10 patients with C.jejuni-associated cellulitis, of whom 6 presented hypogammaglobulinemia. We postulate that the cutaneous manifestations were caused by septic metastases. The immunoglobulin replacement therapy mainly comprised IgG antibodies; IgA and IgM antibodies appear to play a key role in the response to C.jejuni infection, which could explain the susceptibility observed. The American guidelines recommend blood and skin cultures in patients with cellular immune defects. We suggest that this recommendation be extended to patients with humoral immunodeficiency.

X-linked Agammaglobulinemia.

X-linked agammaglobulinemia (XLA) is one of the commonest primary immune deficiencies encountered in pediatric clinical practice. In adults, common variable immunodeficiency (CVID) is the most common primary immunodeficiency disease (PID). It is an X-linked disorder characterized by increased susceptibility to encapsulated bacteria, severe hypergammaglobulinemia and absent circulating B cells in the peripheral blood. Replacement immunoglobulin therapy is the main cornerstone of treatment. Aggressive management of intercurrent infections and prophylactic antimicrobials are needed. This review attempts to highlight varied clinical manifestations and management of XLA, especially in the context of developing country.

Subcutaneous Immunoglobulin Replacement Therapy with Intravenous Preparation in Primary Immunodeficiency Patients

Subcutaneous Immunoglobulin Replacement Therapy with Intravenous Preparation in Primary Immunodeficiency Patients

Use of subcutaneous immunoglobulin in primary immune deficiencies.

Immunoglobulin replacement therapy is required to reduce the frequency and severity of infections in patients with primary antibody deficiencies. Immunoglobulin G (IgG) can be administered intramuscularly, intravenously or subcutaneously. We aimed to evaluate the efficacy, dose adjustment and adverse events in subcutaneous immunoglobulin therapy by retrospectively presenting the records of 16 patients who received subcutaneous immunoglobulin therapy. The demographic findings, clinical and laboratory findings, subcutaneous immunoglobulin dosage and dose frequency, infusion time, area and methods, adverse events and frequency of infections were obtained from patient files and recorded. Sixteen patients (seven female, nine male) aged between 0-33 years who were diagnosed with primary immune deficiency and treated with subcutaneous immunoglobulin were enrolled. All patients had been receiving intravenous imunoglobulin (5-10%) at a dose of 0.33-1.25 gr/kg/dose with two-four week intervals before subcutaneous immunoglobulin. Subcutaneous immunoglobulin (10%) was administered at a dose of 0.03-0.43 gr/kg/dose with one-two week intervals. No significant difference was found between serum through IgG levels before administration of intravenous imunoglobulin and steady state IgG levels during subcutaneous immunoglobulin therapy. When five patients whose serum through IgG levels were below 600 mg/dL were evaluated, however, a significant increase was found in steady state IgG levels with subcutaneous immunoglobulin therapy (p=0.043). In a ten-month follow-up period, seven infections were observed in four patients (three upper respiratory infectons, two lower respiratory tract infections and three acute gastroenteritis). No acute severe bacterial infection was observed. Local advers reaction was reported in only 10 of 180 infusions (6%). No serious adverse events were reported. All 16 patients were willing to continue IgG replacement therapy by subcutaneous administration. Ig replacement therapy by subcutaneous route is an efficient, safe and easy option which is eligible for individual administration. Home therapy is feasible for patients with primary immune deficiency, if informed consent is obtained and sufficient education is ensured.

Autoimmune and Lymphoproliferative Complications of Common Variable Immunodeficiency.

Common variable immunodeficiency (CVID) is frequently complicated by the development of autoimmune and lymphoproliferative diseases. With widespread use of immunoglobulin replacement therapy, autoimmune and lymphoproliferative complications have replaced infection as the major cause of morbidity and mortality in CVID patients. Certain CVID complications, such as bronchiectasis, are likely to be the result of immunodeficiency and are associated with infection susceptibility. However, other complications may result from immune dysregulation rather than immunocompromise. CVID patients develop autoimmunity, lymphoproliferation, and granulomas in association with distinct immunological abnormalities. Mutations in transmembrane activator and CAML interactor, reduction of isotype-switched memory B cells, expansion of CD21 low B cells, heightened interferon signature expression, and retained B cell function are all associated with both autoimmunity and lymphoproliferation in CVID. Further research aimed to better understand that the pathological mechanisms of these shared forms of immune dysregulation may inspire therapies beneficial for multiple CVID complications.

A Canadian perspective on the use of immunoglobulin therapy to reduce infectious complications in chronic lymphocytic leukemia.

Infections are a major cause of morbidity and mortality in patients with chronic lymphocytic leukemia (cll), who typically have increased susceptibility because of hypogammaglobulinemia (hgg) related to their disease and its treatment. Immunoglobulin replacement therapy (igrt) has been shown to reduce the frequency of bacterial infections and associated hospitalizations in patients with hgg or a history of infection, or both. However, use of igrt in cll is contentious. Studies examining such treatment were conducted largely before the use of newer chemoimmunotherapies, which can extend lifespan, but do not correct the hgg inherent to the disease. Thus, the utility of igrt has to be re-evaluated in the current setting. Here, we discuss the evidence for the use of igrt in cll and provide a practical approach to its use in the prevention and management of infections.

Use of Rabies Virus Vaccine As a Neoantigen to Evaluate Humoral Immune Function in Patients with Primary Immunodeficiency Disorders Receiving Immunoglobulin Replacement Therapy

Use of Rabies Virus Vaccine As a Neoantigen to Evaluate Humoral Immune Function in Patients with Primary Immunodeficiency Disorders Receiving Immunoglobulin Replacement Therapy

Clinical and laboratory correlates of lung disease and cancer in adults with idiopathic hypogammaglobulinaemia.

Idiopathic hypogammaglobulinaemia, including common variable immune deficiency (CVID), has a heterogeneous clinical phenotype. This study used data from the national UK Primary Immune Deficiency (UKPID) registry to examine factors associated with adverse outcomes, particularly lung damage and malignancy. A total of 801 adults labelled with idiopathic hypogammaglobulinaemia and CVID aged 18-96 years from 10 UK cities were recruited using the UKPID registry database. Clinical and laboratory data (leucocyte numbers and serum immunoglobulin concentrations) were collated and analysed using uni- and multivariate statistics. Low serum immunoglobulin (Ig)G pre-immunoglobulin replacement therapy was the key factor associated with lower respiratory tract infections (LRTI) and history of LRTI was the main factor associated with bronchiectasis. History of overt LRTI was also associated with a significantly shorter delay in diagnosis and commencing immunoglobulin replacement therapy [5 (range 1-13 years) versus 9 (range 2-24) years]. Patients with bronchiectasis started immunoglobulin replacement therapy significantly later than those without this complication [7 (range 2-22) years versus 5 (range 1-13) years]. Patients with a history of LRTI had higher serum IgG concentrations on therapy and were twice as likely to be on prophylactic antibiotics. Ensuring prompt commencement of immunoglobulin therapy in patients with idiopathic hypogammaglobulinaemia is likely to help prevent LRTI and subsequent bronchiectasis. Cancer was the only factor associated with mortality. Overt cancer, both haematological and non-haematological, was associated with significantly lower absolute CD8(+) T cell but not natural killer (NK) cell numbers, raising the question as to what extent immune senescence, particularly of CD8(+) T cells, might contribute to the increased risk of cancers as individuals age.