INTRODUCTION/AIMS: Prospective, randomized, controlled trials of intravenous immunoglobulin (IVIG) maintenance therapy in myasthenia gravis (MG) are lacking. In this trial, we evaluated the safety and efficacy of caprylate/chromatography-purified IVIG; (IGIV-C) in patients with generalized MG undergoing standard care. METHODS: Sixty-two patients enrolled in this phase 2, multicenter, international, randomized trial (1:1 IGIV-C [2 g/kg loading dose; 1 g/kg every 3 weeks through week 21] or placebo). Efficacy was assessed by changes in Quantitative MG (QMG) score at week 24 versus baseline (primary endpoint) and percentage of patients with clinical improvement in QMG, MG Composite (MGC), and MG-Activities of Daily Living (MG-ADL) scores (secondary endpoints). Safety assessments reported all adverse events (AEs). RESULTS: The change in QMG at 24 weeks was -5.1 for IGIV-C and -3.1 for placebo (p = .187). Seventy percent of patients in the IGIV-C group had improvement in MG-ADL (≥2-point decrease) versus 40.6% in the placebo group (p = .025). Patients showing clinical improvement in QMG and MGC (≥3-point decrease) were 70.0% for IGIV-C versus 59.4% for placebo (p = .442) and 60.0% for IGIV-C versus 53.1% for placebo (p = .610). IGIV-C was well tolerated; serious AEs were similar between arms. Three of four MG exacerbations requiring hospitalizations occurred in the IGIV-C arm with one death. DISCUSSION: Several efficacy parameters showed numerical results greater than those seen in the placebo group. This was a small study and may have been underpowered to see significant differences. Additional studies may be warranted to fully determine the efficacy of IVIG maintenance therapy in MG.

• MeSH
• autoprotilátky krev   MeSH
• činnosti denního života MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• imunologické faktory terapeutické užití   škodlivé účinky   aplikace a dávkování   MeSH
• intravenózní imunoglobuliny * terapeutické užití   škodlivé účinky   aplikace a dávkování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• myasthenia gravis * farmakoterapie   MeSH
• prospektivní studie MeSH
• receptory cholinergní * imunologie   MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

BACKGROUND: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a peripheral nerve disorder characterised by weakness and sensory loss. We assessed the neonatal Fc receptor inhibitor rozanolixizumab for CIDP management. METHODS: CIDP01 (NCT03861481) was a randomised, subject-blind, investigator-blind, placebo-controlled, phase 2a study. Adults with definite or probable CIDP receiving subcutaneous or intravenous immunoglobulin maintenance therapy were randomised 1:1 to 12 once-weekly subcutaneous infusions of rozanolixizumab 10 mg/kg or placebo, stratified according to previous immunoglobulin administration route. Investigators administering treatment and assessing efficacy, and patients, were blinded. The primary outcome was a change from baseline (CFB) to day 85 in inflammatory Rasch-built Overall Disability Scale (iRODS) score. Eligible patients who completed CIDP01 entered the open-label extension CIDP04 (NCT04051944). RESULTS: In CIDP01, between 26 March 2019 and 31 March 2021, 34 patients were randomised to rozanolixizumab or placebo (17 (50%) each). No significant difference in CFB to day 85 in iRODS centile score was observed between rozanolixizumab (least squares mean 2.0 (SE 3.2)) and placebo (3.4 (2.6); difference -1.5 (90% CI -7.5 to 4.5)). Overall, 14 (82%) patients receiving rozanolixizumab and 13 (76%) receiving placebo experienced a treatment-emergent adverse event during the treatment period. Across CIDP01 and CIDP04, rozanolixizumab was well tolerated over up to 614 days; no clinically meaningful efficacy results were seen. No deaths occurred. CONCLUSIONS: Rozanolixizumab did not show efficacy in patients with CIDP in this study, although this could be due to a relatively high placebo stability rate. Rozanolixizumab was well tolerated over medium-to-long-term weekly use, with an acceptable safety profile.

• MeSH
• chronická zánětlivá demyelinizační polyneuropatie * farmakoterapie   MeSH
• dospělí MeSH
• humanizované monoklonální protilátky * terapeutické užití   škodlivé účinky   aplikace a dávkování   MeSH
• intravenózní imunoglobuliny terapeutické užití   škodlivé účinky   MeSH
• jednoduchá slepá metoda MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

BACKGROUND: Dermatomyositis is an idiopathic inflammatory myopathy characterised by rashes and progressive muscle weakness. The recent ProDERM (Progress in DERMatomyositis) study is the first large randomised, placebo-controlled trial to establish the efficacy and safety of intravenous immunoglobulin (IVIg) in adult patients with dermatomyositis. Objectives of this analysis were to closely examine the safety and tolerability of IVIg in patients from the ProDERM study. METHODS: ProDERM was a double-blind, randomised, placebo-controlled, multicentre, phase 3 study. In the first period (weeks 0-16), adults with active dermatomyositis received 2.0 g/kg IVIg (Octagam 10%; Octapharma AG) or placebo every 4 weeks. In the open-label extension period (weeks 16-40), all patients received IVIg for 6 additional cycles; dose reduction (1.0 g/kg) was permitted if patients were stable. Treatment-emergent adverse events (TEAEs) were documented. RESULTS: The 95 patients enrolled were randomised to receive IVIg (N = 47) or placebo (N = 48) in the first period, with 5 switching from placebo to IVIg. Overall, 664 IVIg infusion cycles were administered. During the first period, 113 TEAEs were possibly/probably related to treatment in 30/52 patients (57.7%) receiving IVIg and 38 in 11 patients (22.9%) on placebo. Eight patients discontinued therapy due to IVIg-related TEAEs. Eight thromboembolic events (TEEs) occurred in six patients on IVIg; six in five patients were deemed possibly/probably related to IVIg. Patients with TEEs exhibited more baseline TEE risk factors than those without TEEs (2.4-15.2-fold higher). Lowering infusion rate reduced the rate of TEEs, and none occurred at the lower IVIg dose. No haemolytic transfusion reactions or deaths occurred. CONCLUSIONS: Results from this study demonstrate that IVIg has a favourable safety profile for treatment of adult dermatomyositis patients and provides evidence that will help to inform treatment choice for these patients. Dermatomyositis patients receiving high-dose IVIg should be monitored for TEEs, and a low rate of infusion should be used to minimise TEE risk, particularly in those with pre-existing risk factors. TRIAL REGISTRATION: ProDERM study (NCT02728752).

• MeSH
• dermatomyozitida * farmakoterapie   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• intravenózní imunoglobuliny škodlivé účinky   MeSH
• intravenózní infuze MeSH
• lidé MeSH
• myozitida * chemicky indukované   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

BACKGROUND AND AIMS: The ProCID study evaluated the efficacy and safety of three doses of a 10% liquid intravenous immunoglobulin (IVIg) preparation (panzyga®) in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). This report describes the safety findings. METHODS: Patients were randomised to receive a 2.0 g/kg induction dose followed by maintenance doses of either 0.5, 1.0 or 2.0 g/kg IVIg every 3 weeks over 24 weeks. RESULTS: All 142 enrolled patients were included in the safety analyses. In total, 286 treatment-emergent adverse events (TEAEs) were reported in 89 patients, of which 173 (60.5%) were considered treatment-related. Most TEAEs were of mild severity. Eleven serious TEAEs were reported in 6 patients. Two serious TEAEs in one patient (headache and vomiting) were considered related to treatment, which resolved without study discontinuation. No treatment-related thrombotic events, haemolytic transfusion reactions or deaths occurred. One patient discontinued the study due to a TEAE (allergic dermatitis) probably related to IVIg. Headache was the only dose-dependent TEAE, with incidences ranging from 2.9 to 23.7%, the incidence of all other TEAEs was similar across treatment groups. Most TEAEs were associated with the induction dose infusion, and the rate of TEAEs decreased thereafter. The median (IQR) daily IVIg dose was 78 (64-90) g, and 94.4% of patients tolerated the maximal infusion rate of 0.12 ml/kg/min without pre-medication. INTERPRETATION: Infusions of 10% IVIg at doses up to 2.0 g/kg with high infusion rates were safe and well tolerated in patients with CIDP. CLINICAL TRIAL NUMBERS: EudraCT 2015-005443-14, NCT02638207.

• MeSH
• bolesti hlavy chemicky indukované   MeSH
• chronická zánětlivá demyelinizační polyneuropatie * farmakoterapie   chemicky indukované   MeSH
• intravenózní imunoglobuliny * škodlivé účinky   MeSH
• lidé MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

• MeSH
• hormony kůry nadledvin aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• humanizované monoklonální protilátky terapeutické užití   MeSH
• idiopatická trombocytopenická purpura * diagnóza   patofyziologie   terapie   MeSH
• intravenózní imunoglobuliny aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• lidé MeSH
• receptory thrombopoetinu antagonisté a inhibitory   terapeutické užití   MeSH
• rituximab aplikace a dávkování   terapeutické užití   MeSH
• splenektomie metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• novinové články MeSH

BACKGROUND: Intravenous immune globulin (IVIG) for the treatment of dermatomyositis has not been extensively evaluated. METHODS: We conducted a randomized, placebo-controlled trial involving patients with active dermatomyositis. The patients were assigned in a 1:1 ratio to receive IVIG at a dose of 2.0 g per kilogram of body weight or placebo every 4 weeks for 16 weeks. The patients who received placebo and those without confirmed clinical deterioration while receiving IVIG could enter an open-label extension phase for another 24 weeks. The primary end point was a response, defined as a Total Improvement Score (TIS) of at least 20 (indicating at least minimal improvement) at week 16 and no confirmed deterioration up to week 16. The TIS is a weighted composite score reflecting the change in a core set of six measures of myositis activity over time; scores range from 0 to 100, with higher scores indicating greater improvement. Key secondary end points included at least moderate improvement (TIS ≥40) and major improvement (TIS ≥60), and change in score on the Cutaneous Dermatomyositis Disease Area and Severity Index. RESULTS: A total of 95 patients underwent randomization: 47 patients were assigned to the IVIG group, and 48 to the placebo group. At 16 weeks, 79% of the patients in the IVIG group (37 of 47) and 44% of those in the placebo group (21 of 48) had a TIS of at least 20 (difference, 35 percentage points; 95% confidence interval, 17 to 53; P<0.001). The results with respect to the secondary end points, including at least moderate improvement and major improvement, were generally in the same direction as the results of the primary end-point analysis, except for the change in creatine kinase level (an individual core measure of the TIS), which did not differ meaningfully between the two groups. Over 40 weeks, 282 treatment-related adverse events occurred in the IVIG group, including headache (in 42% of patients), pyrexia (in 19%), and nausea (in 16%). A total of 9 serious adverse events that were considered to be related to IVIG occurred, including 6 thromboembolic events. CONCLUSIONS: In this 16-week trial involving adults with dermatomyositis, the percentage of patients with a response of at least minimal improvement based on a composite score of disease activity was significantly greater among those who received IVIG than among those who received placebo. IVIG was associated with adverse events, including thromboembolism. (Funded by Octapharma Pharmazeutika; ProDERM ClinicalTrials.gov number, NCT02728752.).

• MeSH
• dermatomyozitida * farmakoterapie   terapie   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• intravenózní imunoglobuliny * aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• kreatinkinasa analýza   MeSH
• lidé MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

• MeSH
• anafylaxe patofyziologie   prevence a kontrola   MeSH
• antagonisté histaminu H1 terapeutické užití   MeSH
• cetuximab aplikace a dávkování   škodlivé účinky   MeSH
• dexamethason aplikace a dávkování   MeSH
• intravenózní imunoglobuliny * aplikace a dávkování   škodlivé účinky   MeSH
• intravenózní infuze MeSH
• intravenózní podání metody   normy   škodlivé účinky   MeSH
• léková alergie klasifikace   MeSH
• lidé MeSH
• nežádoucí účinky léčiv klasifikace   MeSH
• premedikace MeSH
• způsoby aplikace léků MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• novinové články MeSH

Imunoglobulinové preparáty jsou plazmatické deriváty obsahující protilátky ve třídě IgG proti širokému spektru antigenů. Jsou podávány intravenózně nebo subkutánně v indikacích substitučních nebo imunomodulačních. Jejich podávání však s sebou také nese riziko nežádoucích reakcí, mezi které patří zejména třesavka, horečka, bolesti hlavy, nauzea, malátnost, bolest svalů, ale i závažnější systémové reakce. Až 1/3 těchto reakcí vzniká v průběhu první aplikace a jejich četnost a tíže závisí na dávce, rychlosti aplikace, způsobu podávání, ale také na komorbiditách léčeného pacienta. Důležitým rizikovým faktorem pro vznik nežádoucích účinků v průběhu aplikace imunoglobulinového preparátu je zejména akutní infekce. Léčba nežádoucích reakcí je obvykle symptomatická.

Immunoglobulin products contain specific antibodies in IgG class which are directed against wide range of pathogens. These products are obtained from plasma of healthy donors. Immunoglobulin derivates can be administrated by intravenous or subcutaneous route in substitution or immunomodulation indications. The administration can be accompanied by a risk of adverse events. The most common are pyretic reactions, chills, headache, nausea, malaise and muscle pain, nevertheless also severe systemic reactions can occur. Almost one third of the reactions appear during the first administration. The number and severity of reactions depends on administered dose, speed and the application way. Pre-existing comorbidities of the patients and presence of acute infection are also an important risk factors for adverse reactions. Therapy of side effects is mostly symptomatic.

• Klíčová slova
• subkutánní imunoglobuliny,
• MeSH
• imunoglobuliny * škodlivé účinky   MeSH
• intravenózní imunoglobuliny * škodlivé účinky   MeSH
• lidé MeSH
• nežádoucí účinky léčiv MeSH
• subkutánní infuze MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

OBJECTIVES: To assess the efficacy and safety of intravenous immunoglobulin (IVIG) 10% (Panzyga® ), a novel human normal IVIG 10%, in patients with chronic immune thrombocytopenia (ITP). BACKGROUND: First-line treatment options in ITP include IVIGs. METHODS: In this prospective, open-label, non-controlled, multicentre, phase III study, patients received a daily dose of IVIG 10% (1 g kg-1 body weight) for two consecutive days. The primary end point was clinical response rate; secondary end points included alternate response definitions, time to response, response duration, platelet counts, regression of bleeding and safety. RESULTS: Forty patients were enrolled (57·5% male, mean age 36·7 years); the full analysis set comprised 36 patients. A clinical response was seen for 29 of 36 patients (80·6%). Median time to response and response duration was 2 days and 14 days, respectively. IVIG 10% was well tolerated at a maximum infusion rate of 8 mg (kg min)-1 in all but one patient; adverse events were mainly mild to moderate in severity, and the most frequent was headache (42·5%). CONCLUSION: IVIG 10% is well tolerated even at a high infusion speed and induces a rapid platelet count increase, thus decreasing the bleeding rate and the severity of bleeding events. TRIAL REGISTRY: ClinicalTrials.gov record: NCT01349790.

• MeSH
• chronická nemoc MeSH
• dospělí MeSH
• idiopatická trombocytopenická purpura krev   farmakoterapie   MeSH
• imunoglobulin G aplikace a dávkování   škodlivé účinky   MeSH
• intravenózní imunoglobuliny aplikace a dávkování   škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• počet trombocytů MeSH
• prospektivní studie MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH

Chronická zánětlivá demyelinizační polyradikuloneuropatie (CIDP) je nejčastější chronická autoimunitní neuropatie. V patogenezi CIDP se účastní jak protilátková, tak i buněčná imunita. Nejčastěji se vyskytuje klasická forma, která se vyznačuje téměř symetrickým klinickým nálezem a multifokálním postižením motorických i senzitivních vláken v elektrofyziologické diagnostice. Terapie CIDP se zahajuje tzv. indukční léčbou, a to kortikosteroidy, intravenózní aplikací vysokých dávek imunoglobulinů (IVIG) či terapeutickou plazmaferézou (TPF). Vzhledem k nárokům na přístrojové vybavení a častějším výskytem nežádoucích reakcí u TPF se v praxi používají kortikoidy či IVIG pro léčbu první volby. IVIG ve srovnání s kortikoidy mívá rychlejší a výraznější terapeutický efekt, který však trvá kratší dobu. Podání IVIG je také podstatně dražší. Nevýhodou dlouhodobé terapie kortikoidy je výskyt nežádoucích vedlejších účinků. Podání IVIG je indikováno jako primární u čistě motorických forem či forem s převahou postižení motorických vláken, u nemocných s kontraindikací kortikoidů a u dětí. Kortikosteroidy jsou primárně indikovány jako indukční terapie u převážné části nemocných s CIDP. Intravenózní podání kortikoidů či opakovaná bolusová perorální terapie jsou zatížena nižším výskytem nežádoucích vedlejších účinků ve srovnání s denním perorálním podáváním kortikoidů.

In pathogenesis of CIDP are primarily of humoral and also cellular immunity. In CIDP, the most frequent is classical form, which is characterized by clinically nearly symmetric and electrophysiologically multifocal impairment of motor and sensory fibers. Therapy of CIDP is initiated by „induction therapy“, consisting of corticosteroids, intravenous administration of high doses of immunoglobulins (IVIG) or therapeutic plasma exchange (TPE). In view of the high demands on the equipment and of more frequent adverse reactions in TPE, the use of corticosteroids or IVIG is the therapy of the first choice. In comparison with steroids the administration of IVIG displays quicker and stronger therapeutic effects, but with shorter duration. Administration of IVIG is also noticeably more expensive. The disadvantage of long lasting steroid therapy is the occurrence of adverse effects. Administration of IVIG is indicated as a first treatment in pure motor forms or in forms with prevailing motor impairment, in patients with contraindication of steroids and in children. Intravenous administration of steroids or repeated oral bolus therapy is associated with a lower occurrence of adverse events in comparison with daily oral corticosteroid therapy.

• MeSH
• chronická zánětlivá demyelinizační polyneuropatie * diagnóza   epidemiologie   farmakoterapie   klasifikace   MeSH
• hormony kůry nadledvin * aplikace a dávkování   škodlivé účinky   MeSH
• intravenózní imunoglobuliny aplikace a dávkování   škodlivé účinky   MeSH
• lidé MeSH
• nežádoucí účinky léčiv MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH