Facilitated subcutaneous immunoglobulin treatment patterns in pediatric patients with primary immunodeficiency diseases.

Aim: This retrospective study investigated real-world hyaluronidase-facilitated subcutaneous immunoglobulin (fSCIG) treatment patterns in pediatric patients with primary immunodeficiency diseases (PIDs) in Poland. Methods: Clinical and demographic information, fSCIG treatment parameters and clinical outcomes were extracted from medical records of 28 participants (aged ≤18 years) with PIDs who received fSCIG. Results: 18 participants (64.3%) started fSCIG with a ramp-up (median duration: 35.5 days). 27 patients (96.4%) were administered fSCIG every 4 weeks and one patient every 3 weeks. 25 patients (89.3%) used one infusion site. No serious bacterial infections occurred. Conclusion: Data support the feasibility of administering fSCIG to children and adolescents with PIDs every 3-4 weeks using a single infusion site and indicate flexibility in modifying fSCIG infusion parameters. Clinical Trial Registration: NCT04636502 (ClinicalTrials.gov).

Antibodies, also known as immunoglobulins, are proteins that are made by the immune system to help fight infections. In primary immunodeficiency diseases (PIDs), part of the immune system may be missing or not working properly. This study looked at the use of an antibody treatment called hyaluronidase-facilitated subcutaneous immunoglobulin (or fSCIG) in Polish children aged 18 years or younger with PIDs. Information on patients, their disease, how fSCIG was being used and how patients responded to treatment was taken from medical records. Out of 28 patients, 18/28 (64.3%) had their fSCIG dose slowly increased, which took an average of 35.5 days. Overall, 27/28 patients were treated with fSCIG every 4 weeks (96.4%), and 25/28 patients used one place to inject fSCIG (89.3%). No serious infections caused by bacteria happened during the study. The study results suggest that children with PIDs could be treated every 3 to 4 weeks with fSCIG, and that flexibility in how fSCIG is injected may offer options suited to individual patients.

Real-world effectiveness and safety of vedolizumab induction therapy for ulcerative colitis: A prospective nationwide Polish observational study.

BACKGROUND: Vedolizumab is recommended as a first-line biological treatment, along with other biological drugs, in ulcerative colitis (UC) patients in whom conventional therapy failed and as a second-line biological treatment following a failure of a tumor necrosis factor alpha (TNF-α) antagonist. OBJECTIVES: We aimed to assess the real-world effectiveness and safety of vedolizumab induction therapy in UC patients treated in the scope of the National Drug Program (NDP) in Poland. MATERIAL AND METHODS: The endpoints were the proportions of patients who reached clinical response, clinical remission and mucosal healing at week 14. Partial Mayo scores, Mayo subscores and C-reactive protein (CRP) levels were also evaluated. RESULTS: Our study population consisted of 100 patients (55 biologic-naïve and 45 biologic-exposed). The median total Mayo score at baseline was 10 (interquartile range (IQR): 9-11), and 52 patients (52%) had extensive colitis. The clinical response at week 14 was achieved in 83 (83%) and clinical remission in 24 (24%) cases. Mucosal healing was observed in 56 (62%) patients at week 14. In patients with prior failure of biologic treatment (n = 25), 17 (68%) responded to vedolizumab treatment. A decrease in the median CRP level (from 3.7 mg/L to 2.6 mg/L) and the median total Mayo score (from 10 to 4) was observed. No new safety concerns were recorded and no patients discontinued the treatment due to adverse events (AEs). CONCLUSIONS: Vedolizumab was effective and safe as induction therapy for UC in a Polish real-world population including patients with severely active UC and a low number of patients with prior biological treatment failures.

Subcutaneous immunoglobulin 20% (Ig20Gly) treatment regimens in pediatric patients with primary immunodeficiencies - real-world data from the IG TATRY study.

BACKGROUND: Subcutaneous administration of immunoglobulins is associated with fewer systemic adverse events and easier infusion compared to intravenous administration. Ig20Gly is a 20% immunoglobulin formulation effective and safe in patients with primary immune deficiency diseases (PIDDs). Real-world data are scarce, therefore our study aimed to examine the real-life treatment regimen and clinical outcomes of Ig20Gly in Polish children with PIDDs. RESEARCHDESIGN: We retrospectively analyzed the medical documentation of 75 pediatric patients aged 0-17 years (mean 9.9) who received Ig20Gly (Cuvitru®; Baxalta US, Inc.; part of Takeda, MA, U.S.A.). RESULTS: The median exposure to treatment of the study population was 22.3 months. At the end of the study, 59 (78.7%) were still on Ig20Gly. The median monthly dose was 0.40 g/kg. The median treatment interval was 7.7 days. Most patients (96%) used one infusion site. The median infusion rate increased with patient age. The median IgG level in the study population, 8.0 g/L, was stable. There was one case of serious bacterial infection. CONCLUSION: This is the largest, long-term real-world study to date on the treatment patterns of Ig20Gly in pediatric patients with PIDDs. The results of this study support the feasibility and tolerability of Ig20Gly usage in PIDD patients across the pediatric age spectrum. TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov (NCT04636502).

Real-world outcomes of 54-week vedolizumab therapy and response durability after treatment discontinuation in ulcerative colitis: results from a multicenter prospective POLONEZ study.

Background: Vedolizumab is a gut-selective anti-lymphocyte trafficking agent used to treat ulcerative colitis (UC) and Crohn's disease. Objectives: We aimed to evaluate the effectiveness, safety, and durability of the therapeutic effect of vedolizumab after treatment discontinuation in a real-world cohort of patients with UC treated in Poland. Design: This was a multicenter, prospective study involving patients with moderate to severely active UC from 12 centers in Poland who qualified for reimbursed treatment with vedolizumab between February and November 2019. Methods: The primary endpoints were clinical response (⩾2-point improvement from baseline on partial Mayo score) and clinical remission (partial Mayo score 0-1), including steroid-free remission, at week 54. Other outcomes included response durability at 26 weeks after treatment discontinuation, identification of predictors of response and remission, and safety assessment. Results: In all, 100 patients with UC were enrolled (55 biologic naïve and 45 biologic exposed). At baseline, 68% of patients were on corticosteroids and 45% on immunomodulators. Clinical response was observed in 62% of patients, clinical remission in 50%, and steroid-free remission in 42.6% at week 54. Within 26 weeks after treatment discontinuation, 37% of patients who maintained response by week 54 relapsed. The decreased number of liquid stools and rectal bleeding and endoscopic response at week 14 were predictive factors for response at week 54. Time from diagnosis ranging 2-5 years, decreased stool frequency, and non-concomitant use of corticosteroids at baseline and at week 14 were predictive factors for remission at week 54. Partial Mayo score < 3 with no subscale score > 1 at week 54 was a predictive factor for durable response after treatment discontinuation. The rate of serious adverse events related to treatment was 3.63 per 100 patient-years. Conclusion: Vedolizumab is effective and safe in UC treatment in Polish patients. However, the relapse rate after the treatment cessation was high. Registration: ENCePP (EUPAS34119).

In Vitro Assays for Diagnosis of Drug-Induced Nonsevere Exanthemas: A Systematic Review and Meta-Analysis.

Frequent mislabelled causal relationship between drug hypersensitivity reactions and culprit drugs reinforces the need for an accurate diagnosis. The systematic reviews and meta-analyses of in vitro assays published so far focused on immediate reactions and the most severe delayed reactions, while the most frequent drug-induced delayed reactions-nonsevere exanthemas-have been underestimated. We aim to fill this gap. A systematic review of studies on in vitro assays used in the diagnosis of nonsevere drug-induced delayed reactions was conducted following the methodology of Preferred Reporting Items for a Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies Statement. The EMBASE and PubMed databases were searched. We have included 33 studies from which we extracted the data, then performed meta-analysis where possible, or synthesised the evidence narratively. The quality of the analysed studies was assessed with the QUADAS-2 tool. The tests identified the most frequently were lymphocyte transformation test (LTT), ELISpot, and ELISA. In the meta-analysis carried out for LTT in reactions induce by beta-lactams, the pool estimate of sensitivity and specificity amounted to 49.1% (95% CI: 14.0%, 85.0%) and 94.6% (95% CI: 81.7%, 98.6%), respectively. The studies showed heterogeneity in study design and laboratory settings, which resulted in a wide range of specificity and sensitivity of testing.

Characteristics of patients with moderate-to-severe ulcerative colitis treated with vedolizumab: results from a Polish multicenter, prospective, observational real-life study (the POLONEZ study).

BACKGROUND: Vedolizumab, a humanized antibody targeting the α4ß7 integrin, was proven to be effective in the treatment of moderate-to-severe ulcerative colitis (UC) in randomized clinical trials. The aim of the POLONEZ study is to determine the demographic and clinical characteristics of the patients with UC treated with vedolizumab within the scope of the National Drug Program in Poland and to assess the real-world effectiveness and safety of vedolizumab in the study population. Here we report the demographic and clinical characteristics of these patients. METHODS: This prospective study included adult patients eligible for UC treatment with vedolizumab who were recruited from 12 centers in Poland between February and November 2019. Collected data included sex, age, disease duration, presence of extraintestinal manifestations or comorbidities, status of previous biologic treatment, and current concomitant treatment. Disease extent was determined according to the Montreal classification, and disease activity was measured with the Mayo Score. RESULTS: A total of 100 (55 biologic-naïve and 45 biologic-exposed) patients were enrolled in the study (51% female, median age 35 years). Among biologic-exposed patients (mostly infliximab-treated), 57% had failed to respond to the therapy. The disease duration was significantly shorter in biologic-naïve (median 5 years) than in biologic-exposed (8 years, p = 0.004) or biofailure patients (7 years, p = 0.04). In the overall population the median Total Mayo Score was 10. Disease extent and activity were similar between the subgroups. CONCLUSIONS: Our study indicates that patients treated with vedolizumab in Poland receive the drug relatively early after UC diagnosis, but their disease is advanced. More than half of the patients had not been treated with biologic drugs before initiating vedolizumab. The study was registered in ENCePP database (EUPAS34119). LAY SUMMARY: Characteristics of patients treated for ulcerative colitis with vedolizumab in Poland Treatment of moderate-to-severe ulcerative colitis (UC) with the integrin antagonist vedolizumab became available within the Polish National Drug Program (NDP) in 2018. In this study, for the first time, we provide detailed demographic and clinical characteristics of 100 patients (median age 35 years, 51% female) treated with vedolizumab in Poland, of whom 55 were biologic-naïve and 45 biologic-exposed. The median duration of disease was 6 years. The disease duration was shorter in biologic-naïve than in biologic-exposed patients. Most patients were affected by extensive colitis (52%) or left-sided colitis (42%). Median disease activity was 10 according to the Total Mayo Score. Sixty-eight patients received concomitant systemic corticosteroids and 45 patients received immunomodulators. Our findings indicate that Polish patients receiving vedolizumab have a high disease activity and are treated relatively early after UC diagnosis. This might be due to the criteria for inclusion of a patient in the NDP.