Long-term Immunotherapy Research Articles

Abstract A08: Application of Miltuximab®-IRDye800 for near-infrared fluorescence imaging of urothelial carcinoma in vivo

Abstract Introduction and Objectives: Up to 50% of patients with non-muscle invasive bladder cancer suffer from recurrence or progression into a muscle-invasive disease despite multiple resections and long-term chemo and immunotherapy. Possible reasons for that are incomplete resection and reimplantation of cancer cells, which could be prevented by early detection and improved resection of tumor margins. Fluorescence-guided surgery is beneficial in some patients with flat tumors; however, it is currently based on metabolic differences of cancer cells and lacks specificity in many cases. Molecular imaging could improve the specificity of fluorescence-guided surgery since it can target biomarkers expressed by individual tumors. We aimed to select a biomarker and develop a probe for molecular imaging of urothelial carcinoma (UC). Methods: One of the biomarkers present in UC is a heparan sulphate proteoglycan Glypican-1 (GPC-1). The anti-GPC-1 monoclonal antibody Miltuximab (Glytherix Ltd. Sydney, Australia) was used to analyze the expression of GPC-1 in UC cell lines T24 and UM-UC-6. Miltuximab was then labelled by a fluorescent dye IRDye800CW and tested in vivo. Luciferase-transfected UM-UC-6 cells were injected subcutaneously into the hind leg of ten nude mice. When the tumors reached 1000 mm3 in volume, the mice were intravenously injected with 5.7 mg/kg Miltuximab-IRDye800 or isotype IgG-IRDye800. They were then imaged daily for ten days and sacrificed for ex vivo imaging to study the distribution of Miltuximab within the body and its accumulation in the tumors. Results: Flow cytometry and Western blotting demonstrated high expression of GPC-1 in cells UM-UC-6 and T24. UM-UC-6 cells formed subcutaneous tumors that were histologically representative of tumors of human bladder in all animals. From one to ten days after the intravenous injection of the fluorescently labeled Miltuximab, we detected its high accumulation in the tumors by in vivo and ex vivo imaging. One day after the injection, tumors could be visualized in both groups with tumor-to-noise (T/N) ratio of 2. On the 5th day, this value went up to 6.7 for Miltuximab and 3.5 for the Isotype IgG group. By day 10, non-bound antibody molecules further cleared from the mice, resulting in T/N ratio of 14.1 in the mice injected with Miltuximab, while in the control group the value reached only 4.8. Conclusions: Overexpression of GPC-1 in UC shows its high potential as a target for molecular imaging. The animal model developed in this study demonstrated accumulation of the antibody in the tumor and its strong visualization, which could be helpful in tumor detection and resection. Another advantage of this platform is its high potential for clinical translation. IRDye800 can be visualized by existing equipment for indocyanine green imaging and has been proven to be safe in several clinical trials. The antibody Miltuximab has also been used in clinic and has an excellent safety profile. Citation Format: Dmitry Polikarpov, Douglas Campbell, Lucinda McRobb, Alexander Zaslavsky, Andrei Zvyagin, Bradley Walsh, Ganesh Palapattu, David Gillatt. Application of Miltuximab®-IRDye800 for near-infrared fluorescence imaging of urothelial carcinoma in vivo [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2019 May 18-21; Denver, CO. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(15_Suppl):Abstract nr A08.

Long-term treatment of Japanese cedar pollinosis with Japanese cedar pollen SLIT drops and persistence of treatment effect: A post-marketing clinical trial

BackgroundThere have been no reports of treatment effect persistence after long-term sublingual immunotherapy (SLIT) in patients with Japanese cedar (JC) pollinosis. Therefore, we conducted a post-marketing clinical trial to investigate the efficacy, safety, and effect persistence of JC pollen SLIT drops after approximately 3 years of treatment. MethodsThis was an open-label trial of 233 patients with JC pollinosis who were treated with JC pollen SLIT drops for approximately 3 years (2015–2017) and followed-up for an additional 2 years (2018–2019). Efficacy and effect persistence were evaluated using nasal and ocular symptom scores, daily use of rescue medication, and Japanese Rhinoconjunctivitis Quality of Life Questionnaire scores recorded during the JC pollen dispersal season of each year. Safety was evaluated by monitoring adverse events and adverse drug reactions. ResultsThe mean combined total nasal symptom and medication score (range 0–18) during the peak symptom periods of 2015 through 2019 were 5.47 ± 3.38, 4.52 ± 3.13, 3.58 ± 2.63, 5.28 ± 4.01, and 6.83 ± 4.65, respectively. The percentage of patients who used no rescue medications during the same periods was 64.8%, 75.2%, 80.3%, 63.7%, and 50.3%, respectively. A total of 138 adverse drug reaction incidents were recorded in 73 of the 233 patients (31.3%), of which 134 incidents (97.1%) were mild in severity. ConclusionsJC pollen SLIT drops demonstrated treatment duration-dependent efficacy with effects that persisted for 2 years after cessation of treatment. The drug had a favorable safety profile over the 5-year study period.

Clinical approach and prognosis of continuous neurological care after intensive care for the patients with severe and refractory anti-N-methyl-D-aspartate receptor encephalitis

Objective: To study the clinical features, continuous care and prognosis of the patients with severe and refractory anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis after intensive care unit (ICU). Methods: Clinical data of patients with severe and refractory anti-NMDAR encephalitis, who were transferred from ICU to general ward of neurology between December 2015 and October 2019, were retrospectively reviewed and analyzed in the study. Results: Twenty patients (11 females and 9 males) were enrolled in the study. The median course of disease when patients were transferred to general ward was 4.4 (2.0, 6.0) months. Six cases were alert, 6 cases were in a coma, 5 were in the early recovery phase and 3 were in the late recovery phase. Severe malnutrition, pneumonia, urinary tract infections, bedsores and leukocytopenia were common complications. Seven out of 18 patients were tested positive for cerebrospinal fluid anti-NMDAR antibodies with high titers (≥1∶100). During this continuous therapy stage,10 patients were treated with intravenous immunoglobulin (IVIg), 1 with methylprednisolone, 2 with rituximab, 1 with intrathecal methotrexate and 1 received intravenous cyclophosphamide. All Patients were prescribed a long-term immunotherapy (mycophenolate mofetil 1.5-3.0 g/d). Sixteen patients (80%) had good prognosis (modified Rankin Scale (mRS)≤2), and the mortality was 10%, with follow-up time of 17.0 (8.0, 27.0) months. Conclusions: Patients with anti-NMDAR encephalitis, who are transferred from ICU, have severely impaired neurologic function. These patients need long-term individualized immunotherapy and continuous neurological care. Good outcomes can be achieved in most patients.

Steroid-sparing maintenance immunotherapy for MOG-IgG associated disorder.

Myelin oligodendrocyte glycoprotein-immunoglobulin G (MOG-IgG) associated disorder (MOGAD) often manifests with recurrent CNS demyelinating attacks. The optimal treatment for reducing relapses is unknown. To help determine the efficacy of long-term immunotherapy in preventing relapse in patients with MOGAD, we conducted a multicenter retrospective study to determine the rate of relapses on various treatments. We determined the frequency of relapses in patients receiving various forms of long-term immunotherapy for MOGAD. Inclusion criteria were history of ≥1 CNS demyelinating attacks, MOG-IgG seropositivity, and immunotherapy for ≥6 months. Patients were reviewed for CNS demyelinating attacks before and during long-term immunotherapy. Seventy patients were included. The median age at initial CNS demyelinating attack was 29 years (range 3-61 years; 33% <18 years), and 59% were female. The median annualized relapse rate (ARR) before treatment was 1.6. On maintenance immunotherapy, the proportion of patients with relapse was as follows: mycophenolate mofetil 74% (14 of 19; ARR 0.67), rituximab 61% (22 of 36; ARR 0.59), azathioprine 59% (13 of 22; ARR 0.2), and IV immunoglobulin (IVIG) 20% (2 of 10; ARR 0). The overall median ARR on these 4 treatments was 0.3. All 9 patients treated with multiple sclerosis (MS) disease-modifying agents had a breakthrough relapse on treatment (ARR 1.5). This large retrospective multicenter study of patients with MOGAD suggests that maintenance immunotherapy reduces recurrent CNS demyelinating attacks, with the lowest ARR being associated with maintenance IVIG therapy. Traditional MS disease-modifying agents appear to be ineffective. Prospective randomized controlled studies are required to validate these conclusions.

A comparative study on clinical characterizations between acute myelitis onset of neuromyelitis optica spectrum disease and idiopathic transverse myelitis

ABSTRACT Background/Aims Both of neuromyelitis optica spectrum disease (NMOSDs) and idiopathic transverse myelitis (ITM) could present as acute transverse myelitis. However, long-term immunological treatment and prognosis are different for high recurrence of NMOSDs. In this study, we summarized clinical differences between acute attack myelitis of NMOSDs and ITM, we further screened serum auto-antibodies to help understand the two distinct clinical entities. Methods This is a retrospective study on 48 NMOSD patients and 49 ITM patients in neurological department of Nanjing Drum Tower Hospital from 2013 to 2019. Clinical, CSF and MRI profiles on the acute episode were also compared between NMOSD patients and ITM patients. Serum AQP4 and auto-antibodies were tested. Clinical parameters were further compared between NMOSD patients with and without auto-antibodies. Results Compared with ITM patients, NMOSD patients manifested with longer vertebral segments (5.42 ± 3.17 segments vs. 2.31 ± 2.36 segments, p < 0.001), higher female/male ratio (13:3 vs. 20:29, p < 0.001), higher IgG index (30.30% vs. 9.09%, p < 0.05). Positive rates of anti-Ro-52 (47.92% vs. 14.29%, p < 0.001), anti-ANAs (50.00% vs.10.20%, p < 0.001) and anti-SSA (35.42% vs. 6.12%, p = 0.001) were significantly higher in the NMOSD patients than the ITM patients. Seropositive Ro-52 and SSA were associated with longer injured spinal cord segments. However, Ro-52 antibody may not be associated with NMOSD relapsing during our follow up. Conclusions NMOSD patients manifested with longer vertebral segments, higher female/male ratio, IgG index, anti-ANAs, anti-Ro-52 and anti-SSA seroprevalence than ITM patients. These features may help clinicians better distinguish NMOSD from ITM and provide long-term immunotherapy reasonably.

Infection-Associated Opsoclonus: A Retrospective Case Record Analysis and Review of Literature.

Opsoclonus, an uncommon clinical sign, and is often described in the context of opsoclonus myoclonus ataxia syndrome (OMAS). OMAS may be paraneoplastic or postinfectious. However, opsoclonus with or without OMAS may occur in association with a wide gamut of infections. Infection-associated opsoclonus/OMAS (IAO) needs recognition as a separate entity, since it demands relatively brief immunosuppression, symptomatic treatment, and has a better outcome. Case records of children, who presented with opsoclonus to a tertiary-care teaching hospital of North India over a period of 1 year (2017-2018), were reviewed. Those with opsoclonus in the setting of an acute infection/febrile illness (symptomatic opsoclonus; IAO) were included. Of 15 children with opsoclonus, 6 children [median age: 42 months (range: 8 months to 7 years); 2 boys] had opsoclonus associated with an infective or febrile illness. Additional clinical findings in these children included myoclonus (n = 2), ataxia (n = 4) and behavioral abnormalities (n = 4). All these patients had an associated neurologic or nonneurologic illness- scrub typhus (n = 1), tuberculous meningitis (n = 1), mumps encephalitis (n = 1), brainstem encephalitis (n = 1), acute cerebellitis (n = 1), and subacute sclerosing panencephalitis (SSPE, n = 1). Children with acute cerebellitis, brainstem encephalitis, and mumps encephalitis were treated with steroids while those with scrub typhus, tuberculosis, and SSPE were treated with antibiotics, antitubercular therapy, and Isoprinosine, respectively. None of them needed long-term maintenance immunotherapy. The evaluation for tumor was negative in all. Three of the 6 children are functionally normal at the last follow-up. Acute neuro infections may trigger opsoclonus. A careful analysis of clinical data and suitable investigations can help differentiate these children from those with OMAS. This distinction may avoid unwarranted long-term immunosuppression.

Significantly increased threshold dose after long-term peanut epicutaneous immunotherapy and daily oral peanut intake

Significantly increased threshold dose after long-term peanut epicutaneous immunotherapy and daily oral peanut intake

Anti-NMDAR encephalitis: A single-center, longitudinal study in China.

ObjectiveTo describe the detailed clinical characteristics, immunotherapy, and long-term outcomes of patients with anti-NMDA receptor (NMDAR) encephalitis in China.MethodsA single-center, prospective study. Patients who met the diagnostic criteria were enrolled from 2011 to 2017 and followed up. The clinical features, treatment, and long-term outcomes were collected prospectively. Factors affecting the long-term prognosis were analyzed.ResultsThe study included 220 patients. The most common clinical presentations were psychosis (82.7%) and seizures (80.9%). Of the patients, 19.5% had an underlying neoplasm; of which ovarian teratoma was 100% of tumors in females and only one male had lung cancer. Most patients (99.5%) received first-line therapy (glucocorticoids, IV immunoglobulin, or plasmapheresis alone or combined), and only 7.3% received second-line immunotherapy (rituximab, cyclophosphamide alone, or combined). Long-term immunotherapy (mycophenolate mofetil or azathioprine >1 year) was administered to 53.2% of patients. During the first 12 months, 207 (94.1%) patients experienced improvement, and 5 (2.3%) died, whereas 38 (17.3%) experienced relapses. At 12-month follow-up, 92.7% had favorable clinical outcomes (modified Rankin Scale score ≤2).ConclusionsPatients in China present with psychosis and seizure frequently but have a low percentage of underlying neoplasms. Re-enforced first-line immunotherapy is effective in managing anti-NMDAR encephalitis in the acute phase. Although relapse is relatively common, with combined first-line and long-term immunotherapy, most patients reached favorable outcomes.

A critical reflection on our first patient presenting with Anti-Nmethyl- D-aspartate receptor encephalitis.

One of the best characterized autoimmune encephalitis is the Anti-Nmethyl- D-aspartate receptor (NMDAR) encephalitis, which may occur in the presence of cancer. First- and second-line immunotherapy and oncological investigations are suggested. We present here a case of an 18-year-old female who was our first patient suffering from Anti- NMDAR encephalitis more than 9 years ago. She was satisfactorily treated with intravenous immunoglobulins and high dose steroid therapy. After more than one year the patient had a relapse. First-line immunotherapy was repeated; however, a complete recovery was achieved only after plasmapheresis. Afterwards, she continued maintenance immunotherapy with steroids for two years and with Azathioprine for about five years associated to regular oncological assessment. In the last years our therapeutical approach of Anti-NMDARencephalitis has significantly changed. Nevertheless, established treatment guidelines are still missing and the role of long-term maintenance immunotherapy is largely unexplored. In addition, oncological revaluation might be indicated in selected patients.

Long-term sublingual immunotherapy for peanut allergy in children: Clinical and immunologic evidence of desensitization

Peanut sublingual immunotherapy (SLIT) for 1year has been shown to induce modest clinical desensitization in allergic children. Studies of oral immunotherapy, epicutaneous immunotherapy, and SLIT have suggested additional benefit with extended treatment. We sought to investigate the safety, clinical effectiveness, and immunologic changes with long-term SLIT in children with peanut allergy. Children with peanut allergy aged 1 to 11years underwent extended maintenance SLIT with 2mg/d peanut protein for up to 5years. Subjects with peanut skin test wheals of less than 5mm and peanut-specific IgE levels of less than 15 kU/L were allowed to discontinue therapy early. Desensitization was assessed through a double-blind, placebo-controlled food challenge (DBPCFC) with up to 5000mg of peanut protein after completion of SLIT dosing. Sustained unresponsiveness was further assessed by using identical DBPCFCs after 2 to 4weeks without peanut exposure. Thirty-seven of 48 subjects completed 3 to 5years of peanut SLIT, with 67% (32/48) successfully consuming 750mg or more during DBPCFCs. Furthermore, 25% (12/48) passed the 5000-mg DBPCFC without clinical symptoms, with 10 of these 12 demonstrating sustained unresponsiveness after 2 to 4weeks. Side effects were reported with 4.8% of doses, with transient oropharyngeal itching reported most commonly. Side effects requiring antihistamine treatment were uncommon (0.21%), and no epinephrine was administered. Peanut skin test wheals, peanut-specific IgE levels, and basophil activation decreased significantly, and peanut-specific IgG4 levels increased significantly after peanut SLIT. Extended-therapy peanut SLIT provided clinically meaningful desensitization in the majority of children with peanut allergy that was balanced with ease of administration and a favorable safety profile.

Outcome of oral immunotherapy for persistent cow's milk allergy from 11years of experience in Finland.

The safety and efficacy of long-term milk oral immunotherapy (OIT) in Finnish children with persistent cow's milk allergy (CMA) were evaluated in an open-label, non-randomized study. During the 11-year study, 296 children aged 5years or older with immunoglobulin E (IgE)-mediated CMA started milk OIT. Follow-up data were collected at three time points: the post-buildup phase, 1year thereafter, and at the cross-sectional long-term follow-up between January 2016 and December 2017. Patients were divided according to baseline milk-specific IgE (sIgE) level and by the amount of milk consumption at the long-term follow-up. The high-dose group consumed ≥2dL of milk daily, while the failure group consumed <2dL of milk or were on a milk-avoidance diet. Out of the initial study group, 244/296 (83%) patients participated in the long-term follow-up. Among these patients, 136/244 (56%) consumed ≥2dL of milk daily. The median follow-up time was 6.5years. Of the recorded markers and clinical factors, the baseline milk sIgE level was most associated with maintaining milk OIT (P<0.001). Respiratory symptoms in the post-buildup phase increased the risk of treatment failure (OR 3.5, 95% CI: 1.5-8.1, P=0.003) and anaphylaxis (OR 14.3, 95% CI: 1.8-114, P=0.01). More than half of the patients were able to maintain the targeted milk dose in their daily diet. Baseline milk sIgE level and reactivity during the early treatment stage strongly predicted the long-term outcome and safety of milk OIT.

An Increase in Tryptase on the First Day of Hymenoptera Venom Immunotherapy Might Be a Predictor of Future Systemic Reactions During Treatment.

Serum tryptase (ST) decreases during long-term venom immunotherapy (VIT). ST also exhibits a circadian variation, with a small decrease after sting challenge. Both findings have been related to successful VIT. Objective: To assess whether variation (increase or decrease) in ST on the first day of VIT is associated with the likelihood of future systemic adverse reactions (SARs) during treatment. We prospectively studied patients who underwent cluster VIT, which was continued for at least 6 months. ST was measured on the first day of VIT, before the first dose (pre-IT tryptase) and after the last dose (post-IT tryptase). Differences between patient groups (with and without SAR) were analyzed. A total of 160 courses of VIT were administered to 150 patients. The median baseline ST value was 4.3 μg/L. A total of 25 courses (15.6%) were associated with SAR. In 64% of the 25 patients with SAR, the post-IT tryptase value was higher than the pre-IT tryptase level; the median increment was 19% in these patients. We found a significant association between the increase in ST on the first day of VIT and future SARs (risk ratio, 7.6). This elevation was independent of the scheduled VIT day, severity of the SAR, and baseline ST value. A slight increase in tryptase on the first day of VIT is an independent variable that is strongly related to a high risk of future SAR. This simple biomarker could improve patient safety.

P3.CR-17 An Interesting Case of Long-Term Immunotherapy Response in Metastatic NSCLC

P3.CR-17 An Interesting Case of Long-Term Immunotherapy Response in Metastatic NSCLC

Clinical and immunological characteristics and predicted factors of vision outcome in patients with acute severe bilateral optic neuritis

Objective: To analyze the clinical and immunological characteristics of acute severe bilateral optic neuritis, and to explore the predictive factors of vision outcome and relapse so as to save visual function and avoid or alleviate vision disability. Methods: Forty-eight inpatients confirmed with acute severe bilateral optic neuritis from January 2013 to June 2015 were included and followed up. The clinical features, immunological findings, optic nerve imaging, visual function outcome and predictors of relapse were statistically analyzed. Results: Acute severe bilateral optic neuritis accounted for 7.3% of the total number of optic neuritis in the same period. There were 35 cases (72.9%) with monophasic course, and 13 cases (27.1%) with recurrence or other central nervous system involvement during the follow-up period; 11 (22.9%) in 48 patients with positive AQP4-IgG; AQP4-IgG-positive patients had a higher recurrence rate (P<0.001) and poorer visual function prognosis (P=0.034) than antibody-negative patients; the baseline visual acuity (P=0.004), early treatment response (P=0.012) and number of involved optic nerve segments (P=0.016) were associated with end point visual function. Positive AQP4-IgG(OR 13.486, 95% CI 1.971-16.263)and combining with other autoimmune antibodies (OR 5.591, 95% CI 1.502-15.621)were independently associated with relapse. Conclusions: Acute severe bilateral optic neuritis is not unusual and may cause blindness or visual disability. The positive rate of AQP4-IgG and the recurrence rate of the disease are low in our study. The necessity for long-term immunotherapy requires individual consideration. The baseline visual acuity, involved segment number of optic nerve and response to early treatment are associated with prognosis of visual function. Patients with AQP4-IgG positive and other autoimmune antibodies are easy to relapse. Whether the antibody-negative bilateral optic neuritis is a heterogeneous disease and the relationship with classic NMO or NMOSD deserve further research.

Bone vascularized composite allotransplantation model in swine tibial defect: Evaluation of surgical angiogenesis and transplant viability.

In prior small animal studies, we maintained vascularized bone allotransplant viability without long-term immunotherapy. Instead, an autogenous neoangiogenic circulation is created from implanted vessels, sufficient to maintain bone viability with only 2 weeks immunosupression. Blood flow is maintained despite rejection of the allogeneic vascular pedicle thereafter. We have previously described a large animal (swine) pre-clinical model, reconstructing tibial defects with vascularized tibial allotransplants. In this manuscript, autologous angiogenesis is evaluated in this model and correlated with bone viability. Allogeneic tibial segments were transplanted across a major swine leukocyte antigen mismatch. Microvascular repair of the bone VCA pedicle was combined with intraosseous implantation of an autogenous arteriovenous (AV) bundle. The bundle was ligated in group 1 (n = 4), and allowed to perfuse in group 2 (n = 4). Three-drug immunotherapy was given for 2 weeks. At 16 weeks micro-CT angiography quantified neoangiogenic vessel volume. Bone viability, rejection grade, and bone healing were analyzed. A substantial neoangiogenic circulation developed from the implanted AV-bundle in group 2, with vessel density superior to ligated AV-bundle controls (0.11 ± 0.05 vs. 0.01 ± 0.01, P = .029). Bone allotransplant viability was also significantly enhanced by neoangiogenesis (78.7 ± 4.4% vs. 27.7 ± 5.8%, P = .028) with higher bone healing scores (21.4 ± 2.9 vs. 12.5 ± 3.7, P = .029). Ligated control tibias demonstrated disorganized bone morphology and higher local inflammation (P = .143). Implantation of autogenous AV bundles into vascularized bone allotransplants resulted in the rapid formation of a neoangiogenic autogenous blood supply in a swine tibia model that maintained bone viability, improved bone healing, and minimized rejection.

Non-Native Conformational Isomers of the Catalytic Domain of PCSK9 Induce an Immune Response, Reduce Lipids and Increase LDL Receptor Levels.

PCSK9 (Proprotein convertase subtilisin/kexin type 9) increases plasma cholesterol levels by promoting LDL receptor degradation. Current antibody inhibitors block the interaction between PCSK9 and LDL receptors, significantly decrease plasma cholesterol levels, and provide beneficial clinical outcomes. To reduce the action of PCSK9 in plasma, a novel strategy that will produce a panel of non-native, conformationally-altered isomers of PCSK9 (X-PCSK9) to develop active immunotherapy targeting of native PCSK9 and inhibiting/blocking the interaction of PCSK9 with LDL receptor, thus decreasing plasma cholesterol levels is proposed. The authors used the scrambled disulfide bond technique to generate conformationally-altered isomers of the catalytic domain of mouse PCSK9. The focus was on the immune response of four X-isomers and their effects on plasma cholesterol and triglyceride levels in both C57BL/6J and Apoe−/− mice. The authors showed that the four immunogens produced significant immunogenicity against native PCSK9 to day 120 after immunization of C57BL/6J and Apoe−/− mice. This resulted in significantly decreased plasma cholesterol levels in C57BL/6J mice, and to a lesser degree in Apoe−/− mice. The X-PCSK9-B1 treated mice had increased LDL receptor mRNA and protein levels at day 120 after treatment. Thus, this study provides a new, potentially promising approach that uses long-term immunotherapy for a treatment of hypercholesterolemia.

P65: EARLY AUSTRALIAN EXPERIENCE WITH THE USE OF A 12‐SQ HDM IMMUNOTHERAPY TABLET

Sublingual house dust mite immunotherapy tablets have been recently introduced for use in Australia. We report early real-life outcomes of a specialist access program with the 12-SQ HDM tablet. Ninety patients with perennial rhinoconjunctivitis commenced treatment that was provided free of cost for the first six months under this program. Data were collected regarding medications used at commencement and at follow up, as well as sneezing frequency and 10-point VAS scores for nasal symptoms and global allergy. Sixty-five of 90 patients returned for a follow-up visit, at 3–4 months. Twenty-five had ceased the treatment, at least eight as a result of adverse effects. Sneezing did appear reduced in frequency at the follow-up visit. Forty-one of 62 patients (66%) had an improvement by at least one point in the VAS nasal symptom severity score at first follow up visit. Before commencing immunotherapy, 43/86 (50%) of individuals were taking oral antihistamines whereas only 21/86 (24%) were using nasal corticosteroids; 22/86 (26%) were using no medical therapy at all. By the first review, antihistamine use had reduced. This real-life data of the use of the 12-SQ HDM tablet in specialist practice in Australia reveals a high early drop out rate despite free treatment; many of these were attributed to adverse effects. Compliance is a major challenge for patients on long-term immunotherapy. For clinicians, appropriate patient selection and education is paramount for the success of this form of treatment. The limited use of standard medical therapy at baseline in this patient group was an unexpected finding. In those that continued immunotherapy, there appeared to be an early signal of benefit.

Expanded phenotypes and outcomes among 256 LGI1/CASPR2-IgG-positive patients.

To describe an expanded phenotypic spectrum and longitudinal outcome in 256 LGI1-IgG-seropositive and/or CASPR2-IgG-seropositive patients. Patients were identified through service neural autoantibody evaluation. Ninety-five had longitudinal follow-up (7-456 months; median = 35). Among 3,910 patients tested, 196 were LGI1-IgG positive, 51 were CASPR2-IgG positive, and 9 were dual positive. Cerebrospinal fluid testing was less sensitive than serum testing, detecting only 24 of 38 (63%) LGI1-IgG-positive and 5 of 6 (83%) CASPR2-IgG-positive patients. LGI1-IgG-positive specimens had higher voltage-gated potassium channel-IgG immunoprecipitation values (0.33nmol/l, range = 0.02-5.14) than CASPR2-IgG-positive specimens (0.10nmol/l, range = 0.00-0.45, p < 0.001). Of patients presenting with pain or peripheral nervous system (PNS) manifestations, 39% were LGI1-IgG seropositive (7% had solely neuropathy or pain). Multivariate analysis identified age as the only significant predictor of central nervous system (CNS) versus PNS involvement (>50 years; odds ratio = 15, p < 0.001). Paroxysmal dizziness spells (PDS), a unique LGI1-IgG accompaniment (14% of patients), frequently delayed the diagnosis. T2-mesiotemporal hyperintensity was more common in LGI1-IgG-positive (41%) than in CASPR2-IgG-positive patients (p = 0.033). T1-bright basal ganglia were confined to LGI1-IgG-positive patients with faciobrachial-dystonic seizures (9 of 39, 31%). Cancer was found in 44% of LGI1-IgG/CASPR2-IgG dual seropositive patients (one-third thymoma). Response to initial immunotherapy was favorable in 97%; mean modified Rankin score was 3 (range = 1-5) at onset and 1.74 (range = 0-6) at last follow-up, with 9% having severe refractory disability, 20% being asymptomatic, 28% receiving immunotherapy, and 58% receiving antiepileptic medication. Older age is a strong predictor of CNS involvement in patients seropositive for CASPR2-IgG or LGI1-IgG. Pain, peripheral manifestations, and stereotypic paroxysmal dizziness spells are common with LGI1-IgG. Response to initial immunotherapy is often favorable, but some patients remain severely disabled, requiring long-term immunotherapy and/or antiepileptic medications. Ann Neurol 2017;82:79-92.

Long-term Walnut Oral Immunotherapy Induces Clinically Relevant Treatment Responses in Tree Nut Allergic Children

Long-term Walnut Oral Immunotherapy Induces Clinically Relevant Treatment Responses in Tree Nut Allergic Children

Efficacy and Safety of Long-Term Epicutaneous Immunotherapy (EPIT) Treatment of Peanut Allergy with Viaskin® peanut: Results of the Two-Year Extension of the Vipes Phase IIb Clinical Trial

Efficacy and Safety of Long-Term Epicutaneous Immunotherapy (EPIT) Treatment of Peanut Allergy with Viaskin® peanut: Results of the Two-Year Extension of the Vipes Phase IIb Clinical Trial