Intravenous Immunoglobulin Infusion Research Articles

Intravenous immunoglobulin therapy for COVID-19 in immunocompromised patients: a retrospective cohort study

ObjectivesTo investigate the effectiveness of intravenous immunoglobulin (IVIG) as treatment for COVID-19 in immunocompromised patients. MethodsThis retrospective study investigated outcomes for immunocompromised, vaccine non-responsive, patients that between September 2022 and April 2023 received IVIG as treatment for COVID-19 in the region of Västerbotten, Sweden. We analyzed clinical data, viral load, and anti-SARS-CoV-2 IgG binding and neutralization levels of patient serum samples and IVIG production batches. Primary and secondary outcomes were clinical cure and viral clearance, respectively. ResultsSixteen patients were analyzed. After a median COVID-19 duration of four weeks, a median 60g IVIG infusion increased SARS-CoV-2 binding and neutralizing antibody levels, with broad in vitro activity against tested variants. The treatment resulted in abrogation of viremia in all patients and general improvement in 15 survivors that all met the primary endpoint. Thirteen patients met the secondary endpoint at follow-up after a median of four months. Two subjects with persistent SARS-CoV-2 carriage relapsed but were successfully retreated with IVIG. ConclusionsAntibodies in IVIG efficiently neutralized several SARS-CoV-2 variants. Treatment with IVIG was associated with clinical cure and viral clearance in immunocompromised patients. Our data suggests that IVIG could be a novel treatment alternative for COVID-19 for this patient category.

Severe Gastrointestinal Complications After IVIG Infusion in Newborns: A Two-Center Study and Literature Review

Background: There are several studies regarding perforations after intravenous immunoglobulin (IVIG) infusion; however, the risk factors are not defined yet. Objectives: The present study aimed to investigate gastrointestinal complications in newborns regarding the reported immunoglobulin A (IgA) levels in IVIG preparations. Methods: This retrospective chart review was conducted on term newborns who received IVIG therapy in two centers in Istanbul. The study included patients with IVIG-associated gastrointestinal bleedings, necrotizing enterocolitis (NEC), and intra-abdominal perforations without any underlying diseases and recorded demographic data (gestational age, birth weight, and gender) and the IgA levels in the IVIG preparations. Infants born below 35 gestational weeks were excluded as they were more likely to have NEC. Results: A total of 71 patients received IVIG therapy, and 15.5% (n = 11) developed major gastrointestinal system (GIS) complications. A total of 36 patients were born ≥ 35 gestational weeks, and gastrointestinal perforation or bleeding occurred in 22.2% (n = 8) of these patients. Two patients died before surgery due to aggressive disease progression. None of these patients had any gastrointestinal symptoms before IVIG therapy or any predisposing factors for gastrointestinal perforation. All patients were on spontaneous breathing and enteral feeding without intolerance. The IgA level content of the IVIG preparations was related to the major GIS complications with strong evidence, and the safe threshold resulted in 14 mg/dL in receiver operating characteristic (ROC) analysis in the present study group. Conclusions: Higher IgA levels in IVIG preparations might be a risk factor for gastrointestinal perforation and bleeding in term newborns. Clinicians should be aware of this potential complication when using IVIG therapy in term newborns and closely monitor for signs and symptoms of major gastrointestinal complications.

Use of human intravenous immunoglobulin for the treatment of 12 dogs with newly diagnosed malignant disease and presumed secondary immune-mediated thrombocytopenia.

To evaluate the safety and efficacy of human intravenous immunoglobulin in dogs with newly diagnosed malignancy and presumed secondary immune-mediated thrombocytopenia. Twelve client-owned dogs with newly diagnosed malignant disease and presumed secondary immune-mediated thrombocytopenia were prospectively enrolled to receive a single infusion of human intravenous immunoglobulin at a dose of 0.5 to 1 mg/kg intravenous over 8 hours. A complete treatment response was defined as a platelet estimation of ≥40,000 platelets/μL within 24 hours and a partial response within 48 hours from the completion of human intravenous immunoglobulin infusion. No treatment response was defined as a platelet estimation remaining <40,000 platelets/μL over 48 hours from the completion of the human intravenous immunoglobulin infusion. This pilot study had a prospective, open-label, uncontrolled design. Out of the 12 enrolled dogs, seven completed the study. A complete treatment response to human intravenous immunoglobulin was identified in one lymphoma dog and a partial response was noted in another lymphoma dog. The remaining 10 dogs had no response to human intravenous immunoglobulin. No clinically relevant adverse reactions to human intravenous immunoglobulin occurred in any of the 12 initially enrolled dogs during the infusion and over a 3-month follow-up period for the seven surviving dogs. The results of this study suggest that the use of human intravenous immunoglobulin in dogs with newly diagnosed malignant disease and presumed secondary immune-mediated thrombocytopenia appears safe, but not effective for the treatment of thrombocytopenia. Larger multi-centre, prospective, double-blinded, placebo-controlled, outcome-based, malignancy-specific studies are needed to further evaluate these preliminary findings.

Safety and tolerability of intravenous immunoglobulin in patients with active dermatomyositis: results from the randomised, placebo-controlled ProDERM study

BackgroundDermatomyositis 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.MethodsProDERM 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.ResultsThe 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.ConclusionsResults 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 registrationProDERM study (NCT02728752).

Safety and tolerability of intravenous immunoglobulin infusion in Down syndrome regression disorder.

Three large multi-center studies have identified the clinical utility of intravenous immunoglobulin (IVIg) in the treatment of Down syndrome regression disorder (DSRD). Yet the tolerability of infusions in individuals with DS and the safety of IVIg remains unknown in this population. This study sought to evaluate the safety and tolerability of IVIg in individuals with DSRD compared to a real-world cohort of individuals with pediatric onset neuroimmunologic disorders. A single-center, retrospective chart review evaluating clinically documented infusion reactions was performed for individuals meeting international consensus criteria for DSRD and having IVIg infusions between 2019 and 2023. Infusion reactions were evaluated for severity and need for alterations in infusion plan. This cohort was compared against an age and sex matched cohort of children with neuroimmunologic conditions who had also received IVIg infusions. In total, 127 individuals with DSRD and 186 individuals with other neuroimmunologic disorders were enrolled. There was no difference in the overall rate of adverse reactions (AEs) between the DSRD and general neuroimmunology cohorts (p = 0.31, 95% CI: 0.80-2.00), but cardiac-related AEs specifically were more common among the DSRD group (p = 0.02, 95% CI: 1.23-17.54). When AEs did occur, there was no difference in frequency of pharmacologic intervention (p = 0.12, 95% CI: 0.34-1.13) or discontinuation of therapy (p = 0.74, 95% CI: 0.06-7.44). There was a higher incidence of lab abnormalities on IVIG among the general neuroimmunology cohort (p = 0.03, 95% CI: 0.24-0.94) compared to the DSRD cohort. Transaminitis was the most common laboratory abnormality in the DSRD group. In a large cohort of individuals with DSRD, there were no significant differences in the safety and tolerability of IVIg compared to a cohort of children and young adults with neuroimmunologic conditions.

The efficacy and safety of intravenous immunoglobulin infusion in 12 h for the initial treatment of Kawasaki disease

BackgroundApproximately 10–20 % of individuals develop a recrudescent or persistent fever after intravenous immunoglobulin (IVIG) infusion for the initial treatment of Kawasaki disease. The aim of this study was to evaluate the efficacy and safety of the initial IVIG treatment of Kawasaki disease based on duration of infusion. MethodsThis retrospective, single-center study included 53 patients with Kawasaki disease who were initially treated with 2 g/kg of IVIG by means of a single infusion from June 2018 to August 2019. We classified patients into two groups based on the duration of the infusion: the 12-h group and the 24-h group. We compared the treatment response of the primary IVIG and its adverse events using the Mann-Whitney U test and Fisher's exact or Chi-square tests. ResultsThere were no significant differences in the response to initial IVIG treatment between the two groups. The duration from treatment onset to defervescence was shorter in the 12-h group than the 24-h group (7 h vs. 12 h, respectively, p = 0.07); however, this was not significant. There were no significant between-group differences regarding adverse events. ConclusionWe concluded that the initial 12-h IVIG treatment was comparable to the 24-h treatment in terms of efficacy and safety. This will enable physicians to feel confident about pursuing a shorter course of treatment with similar results as conventional treatment and decide on administering additional therapy to their patients.

A Paradoxal Reaction from Intravenous Immunoglobulin

Introduction: Intravenous immunoglobulin (IVIG) is among the commonly used agents for many autoimmune conditions, such as chronic inflammatory demyelinating polyneuropathy (CIDP), a progressive neurologic disorder that is characterized by weakness and sensory loss. While rare, adverse effects stemming from IVIG have been noted, these usually occur during or right after the infusion. Hematopoietic adverse events leading to anemia have been documented but are extremely rare. Two cases of IVIG-associated thrombocytopenia have been reported. We present a case of IVIG-induced thrombocytopenia in a patient with CIDP. Case Presentation: A 73-year-old female presented with severe back pain, absent reflexes, worsening sensory loss, and proximal and distal weakness resulting from her CIDP. She received 1000 mg of IV methylprednisolone and 2 grams per kilogram of IVIG (Gamunex) to manage her presenting symptoms. Patient symptoms improved and was subsequently discharged from the hospital. Following the treatment regiment in the hospital she had 2 subsequent infusions of IVIG in the outpatient setting, scheduled 2 weeks apart. On follow up, her platelet count dropped from 333,000 noted at time of hospital discharge to 35,000, 9 days after her second outpatient infusion of IVIG. No known antiplatelet antibodies were found; a formal thrombocytopenic workup for underlying causes was negative. Her count was restored once IVIG was withheld. No other treatment was implemented, and no other changes were made. Discussion: In a retrospective study of patients receiving IVIG, headache and fatigue were the most common adverse reactions. Less frequently, observed events were back pain and changes in blood pressure (mostly tachycardia). Serious complications such as anaphylaxis, infection or cardiac infarction have been noted. Hematological effects such as Coombs negative hypochromic anemia, autoimmune pure red cell aplasia, acute hemolysis, thrombosis, and embolism were stated to be extremely rare. These side effects generally occurred within 6 h after the start of the infusion, and lowering the infusion rate led to an improvement in the symptoms. However, rare late-onset adverse effects (LAe) have been described, none of which describe thrombocytopenia as a possibility. The temporal association between IVIG administration and the rapid decline in this patient's platelet count suggested a possible link. A comprehensive workup excluded common causes of cytopenia, such as viral infections (hepatitis B&amp;C) and nutritional deficiencies (folic acid and copper). The exact mechanism underlying IVIG-induced thrombocytopenia remains unclear. Proposed mechanisms include immune-mediated destruction of platelets or drug-dependent antibody formation. Prompt recognition and appropriate management are crucial to prevent complications associated with severe thrombocytopenia. Our case highlights the significance of monitoring platelet counts in individuals receiving IVIG. Physicians and other providers should know the potential risk of IVIG-induced thrombocytopenia and promptly evaluate any unexplained platelet count decline after infusion. Further research is needed better to understand this rare complication's pathogenesis and risk factors. Heightened vigilance and early intervention can ensure optimal outcomes for IVIG therapy patients. While our patient had no complications from the developed thrombocytopenia, subsequent infusions will be needed for her inevitable CIDP flares. Closer observation and frequent lab draws will be needed to mitigate any future IVIG-associated thrombocytopenia.

Infection Risk and Use of Prophylaxis with Anti-BCMA Bispecific T Cell Engagers and Belantamab Mafodotin for Patients with Relapsed and Refractory Multiple Myeloma

Introduction: BCMA targeted therapies have demonstrated single agent efficacy for patients with triple class exposed or refractory multiple myeloma (RRMM). Teclistamab and Belantamab Mafodotin (Belamaf) are currently approved for RRMM in Europe with several Bispecific T Cell Engagers (TCE) under investigation. However, whilst TCEs have higher response rates and progression free survival to Belamaf, adverse events, particularly infections may influence treatment choice particularly for frailer patients. Intravenous Immunoglobulin (IVIg) is recommended to prevent infections once IgG levels fall &amp;lt;4g/L or even as prophylaxis with anti-BCMA TCEs. Methods: This was a retrospective review of MM patients treated with anti-BCMA monotherapies at University College London Hospitals between 28/07/2015 and 15/06/2023. IVIg was given according to UK guidelines: IgG of &amp;lt;3g/L and recurrent infections/ one severe infection, despite 6 months of prophylactic antibiotics. IgG levels between 3-4g/L also required failure of a vaccine challenge. IVIg for asymptomatic patients was not permitted. Statistics was performed using GraphPad Prism. Results: 55 patients were treated with anti-BCMA monotherapies: 21 with TCE and 34 with Belamaf. The median age was 61 years (range 45-79), 43% female, 80% white and 5.6% Black. The median time from diagnosis to treatment was 5.8 years with a median of 5 prior lines (range 2-15). 51.9% of patients had high risk cytogenetics. Patients were a median of 59 years for TCE (range 47-73) vs 64 years (range 45-79) with Belamaf. Both groups had a median of 5 prior lines and a median Charlson co-morbidity index of 2, but 40% of TCE were classified frail by modified IMWG score vs 61.8% with Belamaf. CD38 exposure was 100% for TCE patients and 76% Belamaf. Severe hypogammaglobulinemia (&amp;lt;4g/L) at baseline prior to anti-BCMA treatment was present in 75% of TCE and 53% of Belamaf patients. Further significant reductions in median IgG levels occurred during treatment (TCE: 3.04g/L to 1.06g/L, p=0.01; Belamaf: 3.9g/L to 1.9g/L p=0.002). Nadir IgG levels were significantly lower with TCE than Belamaf (p=0.047). All patients received aciclovir prophylaxis, PJP prophylaxis (co-trimoxazole/ azithromycin) was given in 100% with TCE and 82% with Belamaf, with anti-fungal prophylaxis in 1 TCE patient. IVIg was used prior to anti-BCMA treatment in 3 patients (2 TCE, 1 Belamaf). Whilst on anti-BCMA treatment, IVIg was used in 38% for TCE and 5.9% for Belamaf. The risk for all grade infection per patient was 3.7 times higher for TCE vs Belamaf (increased risk TCE vs Belamaf: G1-2: 3.3, G3: 2.1, G4: 2.1). There was a total of 104 infection episodes, 57% with TCE, 43% with Belamaf (see Figure). The median time to first infection was 45 days for TCE and 34 days for Belamaf. Most infections were low grade with 20 patients having ≥1 infection (10/21 (48%) TCE, 10/34 (29%) Belamaf). At Grade 1-2, there were 1.8 infections per patient for TCE vs 0.7 for Belamaf. For G3-5, 1.0 infections per patient vs 0.6 for Belamaf. There was 1 grade 5 infection with TCE, 0 for Belamaf. Respiratory infections predominated (TCE: 80% vs Belamaf: 73%) followed by urinary (TCE: 5% vs Belamaf 16%), blood (TCE 10% vs Belamaf 5.4%) and GI (TCE 3% vs Belamaf 5%). 96/ 104 infections were identified, most were viral (TCE 71% vs Belamaf 62%) with few fungal infections (6% vs 4%). More bacterial infections occurred with Belamaf possibly due to lower antibacterial prophylaxis and IVIg use (TCE: 23% vs Belamaf: 35%). Since commencing IVIg, 5 of 8 (63%) TCE patients had at least 1 infection, mainly viral. A median of 1 further infection (range 0-14) occurred over a median of 3.2m (range 0.6-28.3m) of monthly IVIg infusions. Routine blood viral PCR monitoring for CMV, EBV &amp; Adenovirus was performed in 30% of patients. 13 (65%) of TCE patients had 197 blood viral PCR tests performed of which 3 patients (23%) tested positive (2x adenovirus and 1 CMV). Of these 2 (both adenovirus) had symptoms requiring intervention. Of the 8.8% of Belamaf patients tested, 0 were positive. Conclusions: Patients treated with Belamaf were frailer than those receiving TCE. Hypogammaglobulinemia was more profound with TCE and the per patient risk of infections was higher. IVIg use was substantially higher for TCE than Belamaf. Blood viral PCR monitoring for TCE patients only detected symptomatic reactivations in 2 out of 13 patients suggesting this was an infrequent event.

Hypogammaglobulinemia and Infection Risk in Relapsed Refractory B Cell Malignancy Patients Treated with Varnimcabtagene Autoleucel (IMN-003A), a CD19-Directed Chimeric Antigen Receptor T (CAR-T) Cell Therapy, in the Phase-2 Study (IMAGINE)

Background: Varnimcabtagene autoleucel (IMN-003A) is an anti-CD19 CAR-T cell immunotherapy for patients with relapsed refractory B cell malignancies (RR BCM) in the Phase 2 IMAGINE study. Hypogammaglobinemia can result from normal CD19+ B cell depletion (on-target, off-site effect) by CD19 directed CAR-T cells. RR BCM patients (pts) are already at risk for infections due to impaired immune function, lymphodepletion preparative regimen and prior immunosuppressive therapies. Intravenous immunoglobulin (IVIg) replacement is used to reduce the risk of infections due to hypogammaglobulinemia. We report the impact of var-cel on hypogammaglobinemia, infectious complications, risk factors, IVIg usage and clinical outcomes for RR BCM patients treated in first-in-India industry study (CTRI/2022/03/041162). Methods: RR BCM pts treated with var-cel in this study were reviewed. Hypogammaglobulinemia was defined as IgG &amp;lt;4 g/L. Infections reported during pre-apheresis (post screening), D0 to D+28 post CAR-T infusion and beyond D+29 for study duration were analyzed. IVIg usage for hypogammaglobulinemia was at investigator discretion. Patients were monitored for infection events. RR BCM response was assessed as per NCCN (B-ALL) and IWG (B-NHL) criteria. Appropriate statistical tools were used for data analysis. Results: At data cut-off, of 25 pts enrolled (median age 31 yrs, range 3 - 66) with RR BCM (n=13 B-ALL; n=12 B-NHL), 24 pts received var-cel (1 withdrawal). Median follow-up after IMN-003A administration was 205 days (range 12 - 434). Overall response rate (ORR) was 91.7% (22/24) at D+28 (B-ALL 91.7%; B-NHL 91.7%) and 80.9% (17/21) at D+90 (B-ALL 80%; B-NHL 81.8%). Treatment related mortality was 4.2% (n=1/24); 3 pts died of disease progression. Of the 24 pts, none had hypogammaglobulinemia (IgG &amp;lt;4g/L) at baseline. Eleven pts (45.8%) developed hypogammaglobulinemia post var-cel infusion. Of these, 10 pts (90.9%) received prophylactic intravenous immunoglobulin (IVIg). In total, 70.8% (n=17/24) pts received IVIg infusions (Table 1). The median time to initiation of IVIg after var-cel infusion was 58 days (range 15 to 189 days). Of evaluable pts, IVIg was used in 15 of 17 (88.2%) responders at D+90 (CR / PR) vs 0 of 4 (0%) in non-responders (SD / PD) (p=0.06). 52.9% (n=9/17) pts on prophylactic IVIg reported infections. Patients who received IVIg had more infections (30 events; p=0.76). The mean number of infections with and without IVIg was 1.8 and 1.6 respectively. The median overall survival was significantly higher in pts who received IVIg prophylaxis (p=0.02). There was no difference in survival observed based on presence or absence of hypogammaglobulinemia post var-cel infusion (p=0.46). A total of 41 infections were reported in 13 pts. Of these, the incidence from screening to D-1; D0 to D+28 and beyond D+29 were 9 events (4 pts); 12 (11) and 20 (7) respectively. Bacterial, viral and fungal infections reported were 28 events (11 pts); 12 (8) and 1 (1) respectively. Bacterial infections were sepsis (n=7); urinary tract infections (n=5), respiratory (n=14) and central line (n=2). There were 12 viral events, 11 of respiratory origin and one involving conjunctiva. There was one episode of probable fungal candidemia. Stool surveillance detected 27 positive events in 13 pts. Table 2 summarizes the reported infectious organisms. There were 23 infections documented in 13 patients who did not develop hypogammaglobulinemia (median 2 infections; mean 1.8; range 1 - 6). Of 11 pts with hypogammaglobulinemia, there were 18 infections (median 3.5; mean 1.6; range 1 - 9). Complete and partial responders had more infections compared to non-responders (p = 0.05). Conclusions: This is the first-in-India report evaluating hypogammaglobulinemia and infection risk post CAR-T cell infusion. The IVIg usage and documented infections was more in responders. The safety and efficacy outcomes of varnimcabtagene autoleucel (IMN-003A) are consistent with reported outcomes of approved CD19 directed CAR-T cell therapies. The use of prophylactic IVIg, often led by individual practice, to reduce the number of infections and its impact on efficacy outcomes remains uncertain. Potential strategies to reduce infection risk may help improve outcomes.

High occurrence of autoimmune and lymphoproliferative manifestations in adults with common variable immunodeficiency in southernTaiwan.

There are no reported case series of common variable immunodeficiency (CVID) from southern Taiwan. A 20-year review was performed in adult CVID from a southern Taiwan medical center. Patients with ages of 18 years or older were enrolled from May, 2003 to April, 2023. Twelve patients were identified, 8 females/4 males aged 23 to 68 (38.9±13.4) with one to 11 years (5.0±3.3) delay of diagnosis after disease onset. There were concomitant autoimmune disorders in 7 (58 %), splenomegaly in 10 (83%), lymphadenopathy in 4 (25%) and B-cell lymphoma in 2 (17%). All received intravenous immunoglobulin (IVIg) infusion with improved autoimmune-mediated arthritis in 2. Patients with higher IgG trough levels (above 500mg/dL) had a better survival than those with lower IgG trough levels. Adult CVID in southern Taiwan has a high occurrence of autoimmune and lymphoproliferative manifestations. Early diagnosis with IVIg infusion might improve the presentations.

Comparative effectiveness of two intravenous immunoglobulin products in children with Kawasaki disease, a nationwide cohort study

Kawasaki Disease (KD) is the most common acquired pediatric heart disease in the developed world. Rapid infusion of high-dose intravenous immunoglobulin is the standard therapy. Different manufacturing processes of IVIG may influence their efficacy. This study aims to conduct a head to head comparison of two IVIGs, TBSF and Privigen, from a nationwide perspective. The main data source was the National Health Insurance Research Database (NHIRD) of Taiwan. A total of 3368 KD cases involving children under 2 years of age were enrolled from January 2015 to November 2020. The primary endpoint was IVIG resistance, which we defined as the total amount exceeding 26 g in one admission. The secondary endpoints encompassed two distinct criteria: coronary involvement, which was defined as the prolonged use of aspirin or anti-coagulation agents between 180 and 360 days after the index date, and recurrence, which was defined as readmission for IVIG therapy occurring more than 30 days after previous KD index day and continuing until the end of the follow-up period. Privigen demonstrated a lower IVIG resistance rate at 9.4% in comparison to TBSF, which exhibited a rate of 9.7% (odds ratio 0.72, 95% CI 0.52–0.99). Privigen had a lower odds of coronary involvement (odds ratio 0.38, 95% CI 0.18–0.82). There is no difference in recurrence rate (odds ratio 0.60, 95% CI 0.22–1.68). Privigen might have a lower rate of IVIG resistance and reduced coronary artery involvement. The discrepancy may be due to the concentration, the stabilizers, or the source of plasma. Further investigation is needed to compare the effectiveness of different IVIGs in the large randomized controlled clinical trial.

Guillain-Barré Syndrome Following Spinal Fusion Surgery in an Elderly Patient: A Case Report

Guillain–Barré syndrome (GBS) is a rare immune-mediated polyneuropathy that rapidly leads to symmetric, ascending progressive weakness. Although GBS is typically associated with various infectious diseases, such as upper respiratory infections or gastroenteritis, it has also been reported following spine surgery. In this report, the authors present a case of GBS in an elderly patient after spinal fusion surgery and emphasize the importance of evaluating new-onset weakness in such cases. A 79-year-old man with diabetes mellitus and hypertension presented with weakness of the lower extremities and neurogenic claudication with chronic radicular pain. Magnetic resonance imaging revealed anterolisthesis at the L4-L5 level and disc protrusions with central and lateral recess spinal stenosis at L3-L4-L5. Following surgery, the patient complained of weakness and paresthesia in both upper extremities, prompting further investigation. An electrophysiologic study confirmed demyelinating neuropathy and cerebrospinal fluid (CSF) analysis showed elevated viral immunoglobulin levels and albumin-cytological dissociation despite negative bacterial and antiganglioside antibody tests. The patient received intravenous immunoglobulin infusion treatment and showed significant improvement, with full motor function recovery in all extremities after 6 weeks. The authors emphasize the importance of considering GBS in patients experiencing deteriorating neurological symptoms after spine surgery and suggest that electrophysiologic studies and CSF analysis are needed for an accurate diagnosis. Additionally, this report highlights the need for increased vigilance regarding the rapid onset of GBS symptoms in elderly patients following spinal surgery.

Poor Visual Outcome After First Attack in a Cohort of Patients With Myelin Oligodendrocyte Glycoprotein-Related Optic Neuritis.

Myelin oligodendrocyte glycoprotein-associated optic neuritis (MOG-ON) is typically a highly treatable condition that responds quickly to treatment with high doses of corticosteroids. We reviewed the cohort of patients with MOG-ON to identify patients who had poor visual outcome after the first attack despite rapid initiation of treatment. Records of all patients diagnosed with MOG-ON seen in a tertiary neuro-ophthalmology practice were reviewed to identify and describe those with poor visual recovery (final visual acuity of 20/200 or worse in at least one eye) after the first attack despite initiation of treatment within 1 week of symptoms onset. Two patients of 36 fulfilled inclusion criteria: both had bilateral severe optic neuritis at presentation, and both were seen within 7 days of symptoms onset and treated immediately with pulse doses of intravenous corticosteroids followed by very-slow oral taper. Plasma exchange (PLEX) was performed 2 weeks after symptoms onset in both patients because of poor response to steroids, followed by monthly intravenous immunoglobulin infusions. Despite the use of all available treatment modalities, final visual outcome was poor in both patients. In both patients, there was enhancement of intracanalicular portion of optic nerve in the worse-seeing eye. In this cohort of patients with MOG-ON, 2 (5.6%) had very poor visual outcome after the first attack despite immediate initiation of treatment with pulse doses of corticosteroids and subsequent treatment with PLEX. These cases highlight that despite immediate initiation and escalation of treatment, some patients with MOG-ON can have very poor visual outcomes after the initial attack that may be because of the involvement of the intracanalicular portion of the optic nerves.

Anti-Ma2 Antibody-Mediated Paraneoplastic Cerebellar Degeneration and Myeloneuropathy Secondary to Lymphoma.

A 61-year-old woman with a history of untreated low-grade B-cell lymphoma presented with blurry vision, unsteadiness, and worsening pain on touching skin of the upper trunk was enrolled. Blurry vision was attributed to oscillopsia from downbeat nystagmus, which later evolved into macrosaccadic oscillations. MRI brain and spine showed mild, longitudinally extensive T2 hyperintensity in the central gray matter of the spinal cord extending from the medulla to T11 level. Serum paraneoplastic panel was negative; however, she had very high titers of anti-Ma2 antibodies in cerebrospinal fluid. The diagnosis of paraneoplastic neurological syndrome was made. Empiric treatment with high dose of intravenous steroids followed by intravenous immunoglobulin infusions did not improve her symptoms. An extensive search for an underlying tumor commenced and was initially unrevealing. However, two-month follow-up positron emission tomography scan showed increased uptake in a right pulmonary nodule, which when biopsied confirmed diagnosis of extranodal marginal zone lymphoma. The final diagnosis was anti-Ma2 antibody-mediated paraneoplastic cerebellar degeneration and myeloneuropathy secondary to lymphoma.

Subgroups of children with Kawasaki disease: a data-driven cluster analysis.

Although Kawasaki disease is commonly regarded as a single disease entity, variability in clinical manifestations and disease outcome has been recognised. We aimed to use a data-driven approach to identify clinical subgroups. We analysed clinical data from patients with Kawasaki disease diagnosed at Rady Children's Hospital (San Diego, CA, USA) between Jan 1, 2002, and June 30, 2022. Patients were grouped by hierarchical clustering on principal components with k-means parcellation based on 14 variables, including age at onset, ten laboratory test results, day of illness at the first intravenous immunoglobulin infusion, and normalised echocardiographic measures of coronary artery diameters at diagnosis. We also analysed the seasonality and Kawasaki disease incidence from 2002 to 2019 by subgroup. To explore the biological underpinnings of identified subgroups, we did differential abundance analysis on proteomic data of 6481 proteins from 32 patients with Kawasaki disease and 24 healthy children, using linear regression models that controlled for age and sex. Among 1016 patients with complete data in the final analysis, four subgroups were identified with distinct clinical features: (1) hepatobiliary involvement with elevated alanine transaminase, gamma-glutamyl transferase, and total bilirubin levels, lowest coronary artery aneurysm but highest intravenous immunoglobulin resistance rates (n=157); (2) highest band neutrophil count and Kawasaki disease shock rate (n=231); (3) cervical lymphadenopathy with high markers of inflammation (erythrocyte sedimentation rate, C-reactive protein, white blood cell, and platelet counts) and lowest age-adjusted haemoglobin Z scores (n=315); and (4) young age at onset with highest coronary artery aneurysm but lowest intravenous immunoglobulin resistance rates (n=313). The subgroups had distinct seasonal and incidence trajectories. In addition, the subgroups shared 211 differential abundance proteins while many proteins were unique to a subgroup. Our data-driven analysis provides insight into the heterogeneity of Kawasaki disease, and supports the existence of distinct subgroups with important implications for clinical management and research design and interpretation. US National Institutes of Health and the Irving and Francine Suknow Foundation.

Efficacy of intravenous immunoglobulins (IVIg) in improving skin symptoms in patients with dermatomyositis: a post-hoc analysis of the ProDERM study

Dermatomyositis (DM) is a rare autoimmune disease characterized by skin involvement, with or without proximal muscle weakness. Recently, following the ProDERM study, intravenous immunoglobulin (IVIg) was approved for treatment of DM. Until ProDERM evidence from large, placebo-controlled studies supporting its use for dermatological symptoms, was lacking. Here we present efficacy data from ProDERM of IVIg versus placebo for treatment of the cutaneous aspect of DM. ProDERM was a double-blind, randomized, multicenter, Phase 3 study. In the First Period (Weeks 0-16), adults with active DM received 2.0g/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. Cutaneous disease was assessed using measures including modified cutaneous DM disease area and severity index activity (CDASI-A) and damage (CDASI-D) scores, and myositis disease activity assessment tool (MDAAT) including visual analogue scale (VAS). This trial is registered with ClinicalTrials.gov, NCT02728752. The study took place from February 2017 to November 2019. 95 patients received IVIg (N=47) or placebo (N=48) in the First Period. Together, 664 IVIg infusion cycles were administered (median dose, 2.0g/kg). At Week 16, mean CDASI-A change from baseline was-9.36 (95% CI:-12.52,-6.19) in the IVIg group versus-1.16 (-3.32, 0.99) in placebo group (p<0.0001). At the end of the Extension Period, mean changes from baseline were-10.44 (95% CI:-13.94,-6.94) and-10.03 (-13.12,-6.94), respectively. Similar changes were seen for CDASI-D and VAS of MDAAT. These observations were seen regardless of baseline disease severity. ProDERM is the first large prospective, randomized trial to demonstrate the efficacy of IVIg to improve the cutaneous manifestations of DM. IVIg treatment significantly improved dermatological symptoms in patients with DM, regardless of disease severity before treatment, suggesting that IVIg is effective for even the most severe cutaneous DM. This study was sponsored by Octapharma Pharmazeutika Produktionsges m.b.H.

Hospital Readmission Rates in Patients With Neuromyelitis Optica Spectrum Disorder.

Neuromyelitis optica spectrum disorder (NMOSD) is an aggressive central nervous system astrocytopathy often resulting in rapid neurologic decline. Patients have recurrent flares that require immunomodulatory therapy for relapse prevention. These patients are usually hospitalized and may need rehospitalization after decline. Hospital readmission rates are important indicators that can be used to gauge health care quality and have direct implications on hospital compensation. This study aims to identify high-risk characteristics of patients with NMOSD that can be used to predict hospital readmissions. The 2017 Nationwide Readmissions Database was searched for hospital admissions for NMOSD in the United States. All patients with hospital readmission within 30 days of discharge from the index hospitalization were included. The 30-day all-cause readmission rate for NMOSD was 11.9% (95% CI, 10.6%-13.3%). Patients aged 65 to 74 years had higher odds of readmission; those with private insurance had decreased odds. Sex did not affect readmission. Several comorbidities, such as respiratory failure, peripheral vascular disease, neurocognitive disorders, and neurologic blindness, were predictive of readmissions. Plasma exchange increased the odds of readmission, whereas intravenous immunoglobulin and immunomodulatory infusions, such as chemotherapies and monoclonal antibodies, did not affect readmission. The most common etiologies for 30-day read-mission were neurologic, infectious, and respiratory. Treatment targeted toward these etiologies may result in reduced overall readmission, thereby decreasing overall disease burden.

Safety of Intravenous Immunoglobulin Replacement Therapy in a Group of Patients with Primary Immune Deficiency

Background Intravenous immunoglobulin (IVIG) has been used as antibody replacement therapy in primary immunodeficiency diseases for more than 50 years. Most routinely, IVIG is used in patients with predominantly antibody deficiency and combined immunodeficiency. Aim To evaluate the safety of regular intravenous immunoglobulin (IVIG) among patients with primary immunodeficiency diseases who receive IVIG as a replacement treatment. Methods Our study included 40 patients with primary immunodeficiency following up regularly in the Pediatric Allergy and Immunology Unit, Children’s Hospital, Ain Shams University, These patients were followed up for one year in order to evaluate the incidence of occurrence of adverse reactions among the patients who received IVIG monthly, Once patients with adverse reactions have been identified, the following data were taken and reviewed : a specific type of adverse reaction to IVIG; the time interval between onset of adverse reaction and beginning of IVIG infusion; IVIG preparation, dose and infusion rate; medical management done during side effects . Statistics were used to analyze and interpret the data. Results This study included 40 PID patients. They were 31 males (77.5%) and 9 females 22.5% with a male to female ratio of 3.4:1. At time of enrolment in the study, the median age was 73.5 months (14 – 218 months). In our studied population the median age of symptoms onset was 23 months (1 – 187 months), and age at diagnosis was 25 months (2-192 months). This made the diagnostic lag to have a median of 9 months (0-56 months). From our studied population only one patient (2.5%) out of the study groups developed anaphylaxis and was shifted to another brand. Conclusion IVIG is a safe drug for patients with primary antibody deficiency with minimal reported side effects.

Serum neurofilament light chain does not detect self-reported treatment-related fluctuations in chronic inflammatory demyelinating polyneuropathy.

Serum neurofilament light chain (sNfL) is a marker for axonal degeneration. Patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) often report a fluctuation of symptoms throughout one treatment cycle with intravenous immunoglobulins (IVIG). The aim of this study was to determine whether sNfL is suitable to quantify patient-reported symptom fluctuations. Twenty-nine patients with the diagnosis of CIDP or a CIDP-variant under treatment with IVIG were recruited in this study and underwent examination before IVIG infusion, in the middle of the treatment interval, and before their next IVIG infusion. Patients were surveyed regarding symptom fluctuations at the last visit and divided into two groups: those with and without fluctuations of symptoms. At the first visit, sociodemographic and disease-specific data were collected. Clinical scores were assessed at every examination. sNfL values were compared between both groups at the different time points after conversion into Z-scores-adjusted for age and body mass index. Patients with CIDP show elevated sNfL Z-scores (median at baseline: 2.14, IQR: 1.0). There was no significant change in sNfL Z-scores or questionnaire scores within the treatment cycle in either group. There was no significant difference in sNfL levels between the patients with and without symptom fluctuations. CIDP patients show elevated sNfL levels. However, sNfL is not suitable to reflect patient-reported fluctuations of symptoms. This indicates that symptom fluctuations during treatment with IVIG in patients with CIDP are not caused by a neuroaxonal injury. Furthermore, repeated sNfL measurements within one treatment cycle with IVIG seem to have no benefit for symptom monitoring.

A retrospective analysis of haemolytic reactions to intravenous immunoglobulin using data from the Transfusion-Transmitted Injuries Surveillance System (Ontario).

Haemolysis can occur following intravenous immunoglobulin (IVIG) infusion. Haemovigilance data were analysed using a novel approach for including two control groups with no haemolysis to IVIG. Objectives included a summary of all reactions to IVIG, rate estimates and analysis of haemolytic reactions including risk factors. Canadian haemovigilance data from Ontario (2013-2021), IVIG distribution and transfusion data from the blood supplier, and data from a large local transfusion registry were used. An 'other-reactions' control group included patients with IVIG reactions that were not haemolytic, and registry patients with no-reaction were the 'no-reaction controls'. Descriptive analysis and two logistic regression models for the different control groups were performed. One thousand one hundred and seventy reactions were included. Most common were febrile non haemolytic (26.1%), minor allergic (24.5%) and IVIG headache (15.3%) followed by haemolytic 10.9% (128/1170). Haemolytic reaction rates decreased over time: rates since 2020 estimated between 1.5 and 2.9/1000 kg IVIG used. The regression model for other-reaction controls identified two risk factors for haemolysis: non-O blood group recipients compared with group O recipients (p value = 0.0106) and IVIG dose per 10 g increase (OR 1.359; 95% CI 1.225-1.506). The model using no-reaction controls gave similar results and also showed no pre-medication was associated with a higher risk of haemolysis (OR 29.084; 95% CI 1.989-425.312). The frequency of haemolytic reactions has decreased over time. We confirmed non-O blood group recipients and IVIG dose as risk factors for haemolysis and raise the hypothesis that no pre-medication may increase the risk of haemolysis.