Subcutaneous immunoglobulin replacement therapy in a patient with 18q deletion syndrome, primary immune deficiency, and type 1 diabetes.
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SUBMITTER: Hogendorf A
PROVIDER: S-EPMC8442480 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:PurposeImmunoglobulin (Ig) replacement therapy is an important life-saving treatment modality for patients with primary antibody immune deficiency disorders (PAD). IVIG and SCIg are suitable alternatives to treat patients with PAD but vary in key ways. Existing evidence on patient preferences for Ig treatments given the complexities associated with IVIG and SCIg treatment is limited and fails to account for variations in preferences across patients. For this reason, we sought to evaluate PAD patient preferences for features of IVIG and SCIg across different patient characteristics.Materials and methods119 PAD patients completed a discrete-choice experiment (DCE) survey. The DCE asked respondents to make choices between carefully constructed treatment alternatives described in terms of generic treatment features. Choices from the DCE were analyzed to determine the relative influence of attribute changes on treatment preferences. We used subgroup analysis to evaluate systematic variations in preferences by patients' age, gender, time since diagnosis, and treatment experience.ResultsPatients were primarily concerned about the duration of treatment side effects, but preferences were heterogeneous. This was particularly true around administration features. Time since diagnosis was associated with an increase in patients' concerns with the number of needles required per infusion. Also, patients appear to prefer the kind of therapy they are currently using which could be the result of properly aligned patient preferences or evidence of patient adaptive behavior.ConclusionsHeterogeneity in preferences for Ig replacement treatments suggests that a formal shared decision making process could have an important role in improving patient care.
| S-EPMC8854788 | biostudies-literature
Project description:BackgroundPatients with chronic lymphocytic leukemia (CLL) experience hypogammaglobinemia and non-neutropenic infections. In this exploratory proof of concept study, our objective was to determine the prevalence of humoral immunodeficiency in patients with CLL and serum IgG ≥ 400 mg/dL, and to evaluate the efficacy of subcutaneous immunoglobulin (SCIG) in this population.Patients and methodsPatients with CLL with serum IgG ≥ 400 mg/dL were evaluated for serum IgG, IgM, IgA, along with pre/post vaccine IgG titers to diphtheria, tetanus, and Streptococcus pneumoniae. Patients with evidence of humoral dysfunction were treated with SCIG with Hizentra every 7±2 days for 24 weeks.ResultsFifteen patients enrolled with median IgG = 782 mg/dL [IQR: 570 to 827], and 6/15 (40%) responded to vaccination with Td, while 5/15 (33%) responded to vaccination with PPV23. 14/15 (93.3%) demonstrated humoral immunodeficiency as evidenced by suboptimal vaccine responses, and were treated with SCIG. In patients treated with SCIG, serum IgG increased from 670 mg/dL [IQR: 565 to 819] to 1054 mg/dL [IQR: 1040 to 1166] after 24 weeks (95% CI: 271-540). For streptococcus pneumoniae, the median protective serotypes at baseline was 8 [IQR: 4 to 9] and increased to 17 [IQR: 17 to 19] after 24 weeks (95% CI: 6.93-13.72). Non-neutropenic infections (NNI) decreased from 14 to 5 during treatment with SCIG.ConclusionsPatients with CLL demonstrate humoral immunodeficiency despite IgG > 400 mg/dL. For these patients, SCIG is well tolerated and efficacious in improving serum IgG, specific IgG to streptococcus pneumoniae, and may decrease reliance on antibiotics for the treatment of NNIs.Clinical trials registrationNCT03730129.
| S-EPMC8519417 | biostudies-literature
Project description:BackgroundPatients with an IgG subclass deficiency (IgSD) ± specific polysaccharide antibody deficiency (SPAD) often present with recurrent infections. Previous retrospective studies have shown that prophylactic antibiotics (PA) and immunoglobulin replacement therapy (IRT) can both be effective in preventing these infections; however, this has not been confirmed in a prospective study.ObjectiveTo compare the efficacy of PA and IRT in a randomized crossover trial.MethodsA total of 64 patients (55 adults and 9 children) were randomized (2:2) between two treatment arms. Treatment arm A began with 12 months of PA, and treatment arm B began with 12 months of IRT. After a 3-month bridging period with cotrimoxazole, the treatment was switched to 12 months of IRT and PA, respectively. The efficacy (measured by the incidence of infections) and proportion of related adverse events in the two arms were compared.ResultsThe overall efficacy of the two regimens did not differ (p = 0.58, two-sided Wilcoxon signed-rank test). A smaller proportion of patients suffered a related adverse event while using PA (26.8% vs. 60.3%, p < 0.0003, chi-squared test). Patients with persistent infections while using PA suffered fewer infections per year after switching to IRT (2.63 vs. 0.64, p < 0.01).ConclusionWe found comparable efficacy of IRT and PA in patients with IgSD ± SPAD. Patients with persistent infections during treatment with PA had less infections after switching to IRT.Clinical implicationGiven the costs and associated side-effects of IRT, it should be reserved for patients with persistent infections despite treatment with PA.
| S-EPMC7858555 | biostudies-literature
Project description:Secondary antibody deficiency can occur as a result of haematological malignancies or certain medications, but not much is known about the clinical and immunological features of this group of patients as a whole. Here we describe a cohort of 167 patients with primary or secondary antibody deficiencies on immunoglobulin (Ig)-replacement treatment. The demographics, causes of immunodeficiency, diagnostic delay, clinical and laboratory features, and infection frequency were analysed retrospectively. Chemotherapy for B cell lymphoma and the use of Rituximab, corticosteroids or immunosuppressive medications were the most common causes of secondary antibody deficiency in this cohort. There was no difference in diagnostic delay or bronchiectasis between primary and secondary antibody deficiency patients, and both groups experienced disorders associated with immune dysregulation. Secondary antibody deficiency patients had similar baseline levels of serum IgG, but higher IgM and IgA, and a higher frequency of switched memory B cells than primary antibody deficiency patients. Serious and non-serious infections before and after Ig-replacement were also compared in both groups. Although secondary antibody deficiency patients had more serious infections before initiation of Ig-replacement, treatment resulted in a significant reduction of serious and non-serious infections in both primary and secondary antibody deficiency patients. Patients with secondary antibody deficiency experience similar delays in diagnosis as primary antibody deficiency patients and can also benefit from immunoglobulin-replacement treatment.
| S-EPMC4074074 | biostudies-literature
Project description:BackgroundHospital-based intravenous immunoglobulin (IVIg) treatment has been the standard treatment mode for patients with primary immunodeficiency disease (PID). With the newer home-based subcutaneous immunoglobulin (SCIg) becoming approved for use in most countries, the question arises as to whether SCIg is a cost-effective treatment mode compared to IVIg in Australia.Materials and methodsWe developed a Markov cohort simulation model with six health states: PID without infection, PID with infection treated at home or hospital, bronchiectasis without infection, bronchiectasis with infection treated at home or hospital, bronchiectasis with chronic Pseudomonas aeruginosa infection, and death, from an Australian healthcare system perspective. A 10-year time horizon with weekly cycles was chosen, and the expected costs and quality-adjusted life-years (QALYs) of the two treatment options estimated.ResultsThe cumulative 10-year cost per patient was 297,547 Australian dollars (A$) with IVIg and A$ 251,713 for SCIg. IVIg resulted in 5.55 QALYs and SCIg 5.57 QALYs. Thus, SCIg appears to be a cost-saving option and possibly improves QALY from the Australian healthcare system perspective (i.e., the dominant treatment option). A probabilistic sensitivity analysis showed that the SCIg option is preferred in 93.2% of simulations given willingness to pay of A$ 50,000 per QALY gained.DiscussionThe results suggest that home-based SCIg is a cost-effective treatment option for patients with PID in Queensland, Australia.
| S-EPMC7141942 | biostudies-literature
Project description:BackgroundAdult antibody deficiency remains under-recognised and under-studied - especially among Asian populations. Patterns of immunoglobulin use and the feasibility of subcutaneous immunoglobulin (SCIg) replacement among Chinese patients remains unclear.ObjectiveTo investigate the trends of immunoglobulin use, burden of adult antibody deficiency and the outcomes of patients on SCIg compared to intravenous immunoglobulin (IVIg) replacement in Hong Kong through a retrospective observational study.MethodsPopulation-wide data of immunoglobulin recipients in Hong Kong between 2012 and 2021, and longitudinal clinical data of adult immunodeficiency patients at Queen Mary Hospital were collected and analysed.ResultsTotal immunoglobulin consumption and recurrent immunoglobulin recipients increased continuously from 175,512g to 298,514g (ρ=0.99, p<0.001) and 886 to 1,508 (ρ=0.89, p=0.001) between 2012-21 in Hong Kong. Among 469 immunoglobulin recipients at Queen Mary Hospital in 2021, 344 (73.3%) were indicated for replacement. Compared to those on IVIg (n=14), patients on SCIg replacement (n=8) had fewer immunodeficiency-related hospitalisations (IRR=0.11) and shorter duration of hospitalisation stay (IRR=0.10) per year, as well as better quality of life (SF-36v2 Health Survey and Life Quality Index). Estimated annual healthcare cost of SCIg replacement per patient was lower than that of IVIg (HKD196,850 [USD25,096] vs HKD222,136 [USD28,319]).ConclusionThere was a significantly increasing burden of adult antibody deficiency and immunoglobulin consumption in Hong Kong. SCIg was feasible and more cost-effective when compared to IVIg, with SCIg patients experiencing better clinical outcomes and quality of life. Future prospective studies to confirm the long-term efficacy and superiority of SCIg are required.
| S-EPMC9795180 | biostudies-literature
Project description:Patients with primary or secondary antibody deficiency (PAD or SAD) are at increased risk of recurrent infections that can be alleviated by immunoglobulin replacement therapy (IRT). In addition to replenishing antibody levels, IRT has been suggested to modulate immune response in patients with antibody deficiency. Although both commonly treated with IRT, the underlying causes of PAD and SAD vary greatly, suggesting differential modulation of T-cell function that may lead to different responses to IRT. To explore this, peripheral blood mononuclear cells (PBMCs) were sampled from 17 PAD and 14 SAD patients before and 2-10 months after initiation of IRT, and analyzed for changes in T-cell phenotype and function. Proportions of CD4, CD8, Treg, or memory T-cells did not significantly change post-IRT compared to pre-IRT. However, we report distinct modulation in T-cell function between PAD and SAD patients post-IRT. Upon α-CD3/CD28 stimulation, proportion of IFN-γ+ CD4 and CD8 T-cells increased in SAD (p = 0.005) but not PAD patients post-IRT compared to baseline. Interestingly, total T-cell proliferation was reduced post-IRT in both PAD and SAD patients, although the reduction in proliferation was primarily due to reduced CD4 T-cell proliferation in PAD (p = 0.025) in contrast to CD8 T-cells in SAD (p = 0.042). In summary, even though IRT provides patients with passive humoral immunity-mediated protection in PAD and SAD, our findings suggest that IRT immunomodulation of T-cells is different in T-cell subsets depending on underlying immunodeficiency.
| S-EPMC6793872 | biostudies-literature
Project description:The genes encoding the variable (V) region of the B-cell antigen receptor (BCR) are assembled from V, D (diversity), and J (joining) elements through a RAG-mediated recombination process that relies on the recognition of recombination signal sequences (RSSs) flanking the individual elements. Secondary V(D)J rearrangement modifies the original Ig rearrangement if a nonproductive original joint is formed, as a response to inappropriate signaling from a self-reactive BCR, or as part of a stochastic mechanism to further diversify the Ig repertoire. VH replacement represents a RAG-mediated secondary rearrangement in which an upstream VH element recombines with a rearranged VHDHJH joint to generate a new BCR specificity. The rearrangement occurs between the cryptic RSS of the original VH element and the conventional RSS of the invading VH gene, leaving behind a footprint of up to five base pairs (bps) of the original VH gene that is often further obscured by exonuclease activity and N-nucleotide addition. We have previously demonstrated that VH replacement can efficiently rescue the development of B cells that have acquired two nonproductive heavy chain (IgH) rearrangements. Here we describe a novel knock-in mouse model in which the prerearranged IgH locus resembles an endogenously rearranged productive VHDHJH allele. Using this mouse model, we characterized the role of VH replacement in the diversification of the primary Ig repertoire through the modification of productive VHDHJH rearrangements. Our results indicate that VH replacement occurs before Ig light chain rearrangement and thus is not involved in the editing of self-reactive antibodies.
| S-EPMC4321307 | biostudies-literature
Project description:Facilitated subcutaneous immunoglobulin (fSCIG) replacement therapy is the latest method of IgG administration; however, real-life data are limited. We retrospectively analyzed the everyday experience of fSCIG administration, particularly, the method used to switch from intravenous immunoglobulin (IVIG) or subcutaneous immunoglobulin (SCIG) to fSCIG and the dosing modifications required. Of the 39 adult patients with primary immunodeficiency (PID) who received fSCIG, 34 remained on the therapy at the end of the study. The median observation time was 18 (range, 3-24) months. Two patients were IgG-treatment-naïve; 23 had previously received IVIG and 14 had received SCIG. In 25 cases, a non-ramp-up dosing mode was used to switch to fSCIG (including two half-monthly doses given biweekly in 14 cases, and full monthly doses given in 11 cases), a ramp-up mode was used in six cases; other methods were used in eight cases. The median IgG trough level at baseline was 7.9 g/L (n = 38), 7.9 g/L (n = 32) at Month 6, 9.0 g/L (n = 30) at Month 12, 8.6 g/L (n = 22) at Month 18, and 9.0 g/L (n = 11) at Month 24. No serious bacterial infections or hospitalizations due to PID complications occurred. At the end of the study, 24 patients (71%) received fSCIG every 4 weeks, six (18%) received fSCIG every 3 weeks, and four (12%) received fSCIG biweekly. In conclusion, our study provides real-life evidence of clinical efficacy of personalized fSCIG treatment when switching from prior immunoglobulin replacement using various switching modes and dosing frequencies.
| S-EPMC7326142 | biostudies-literature
Project description:PurposePrimary immunodeficiency diseases (PIDDs) are a heterogenous group of disorders characterized by intrinsic impairment in the immune system. Most patients with PIDD require life-long immunoglobulin G replacement therapy, which has been shown to reduce the rate of infections and, related hospitalizations and reduce health-related quality of life (HRQOL). Here, treatment satisfaction and HRQOL in patients with PIDD was evaluated upon switching from intravenous (IVIG) or subcutaneous immunoglobulins (SCIGs) to 20% SCIG (Hizentra®), and during long-term steady-state Hizentra® treatment.MethodsAnalyses were based on two pivotal (switch) and four extension/follow-up (maintenance) Phase III studies of Hizentra® conducted in Europe (EU), Japan (JP), and the United States (US). Two validated questionnaires were used: Life Quality Index (LQI) for assessment of IgG-specific perceptions of HRQOL and Short Form 36 version 2 (SF-36v2).ResultsIn the EU and JP switch studies, there was significant and meaningful improvement from Screening in LQI domain scores at all time points, largely driven by patients switching from IVIG to SCIG. In the EU switch study, there were also significant increases in mean SF-36v2 domain scores for Physical Function and General Health from Screening to Week 12. These improvements were observed also at Week 24. Overall, LQI and SF-36v2 domain scores were generally sustained in the maintenance studies.ConclusionsThese results showed that switching patients from IVIG to SCIG improves patient self-reported health status and IgG-specific HRQOL perception. The maintenance studies generally showed no deterioration of this improved health status over a long follow-up period.
| S-EPMC6292975 | biostudies-literature