AChR Ab Research Articles

Time to response with ravulizumab, a long-acting terminal complement inhibitor, in adults with anti-acetylcholine receptor antibody-positive generalized myasthenia gravis.

The efficacy and safety of ravulizumab, a terminal complement C5 inhibitor, in adults with anti-acetylcholine receptor antibody-positive (AChR Ab+) generalized myasthenia gravis (gMG) were demonstrated in the CHAMPION MG study (NCT03920293). This analysis aimed to characterize the latency to onset of a clinically meaningful therapeutic effect for ravulizumab. Post hoc analysis of data collected for up to 60 weeks from CHAMPION MG was performed to assess the timing of response to ravulizumab. Response was analyzed based on reductions of ≥2 and ≥3 points (minimal clinically important differences [MCIDs]) in Myasthenia Gravis-Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) total scores, respectively, and on more rigorous reductions of ≥3 and ≥5 points, respectively. Time to first response was assessed using the Kaplan-Meier product-limit method. The median (95% confidence interval) time to first response was 2.1 (2.1-2.6) and 4.1 (2.3-10.0) weeks for reductions of ≥2 and ≥3 points in MG-ADL total score, respectively (n = 139), and 4.1 (2.1-10.0) and 18.3 (11.0-33.4) weeks for reductions of ≥3 and ≥5 points in QMG total score, respectively (n = 134). Cumulative response rates at Week 60 (data cut-off) were 88% and 82% for ≥2- and ≥3-point MG-ADL score reductions, respectively, and 86% and 59% for ≥3- and ≥5-point QMG score reductions, respectively. The median times to MCID with ravulizumab treatment in patients with AChR Ab+ gMG were ~2 weeks and ~4 weeks based on MCID MG-ADL and QMG total score reductions, respectively.

Analysis of clinical features and outcomes in patients with ocular myasthenia gravis according to anti-acetylcholine receptor antibody-seropositivity.

To comparatively analyze the clinical characteristics of patients with ocular myasthenia gravis (OMG) referred to an ophthalmology clinic, according to anti-acetylcholine receptor antibody (AchR Ab)-seropositivity. Retrospective Cohort Study. Medical records of patients with OMG who presented to a tertiary eye care center between 2003 and 2020 were retrospectively reviewed. Demographics, ophthalmologic characteristics, response to medical treatment, presence of autoimmune thyroid disease and thyroid autoantibody were compared between the AchR Ab seropositive and seronegative groups. A total of 130 patients with OMG were identified; among them, 46 patients (35.4%) had autoantibody against acetylcholine receptors. The mean age at symptom onset was 42.4 ± 18.9 years. There were no differences in mean age at symptom onset, gender ratio, and mean follow-up period between patients with seropositive and seronegative OMG. Graves ophthalmopathy was significantly more frequent in seronegative patients (p = 0.04), while thymic disease (p < 0.01) was more frequent in seropositive patients (p < 0.01). Among patients with seropositive OMG, 52.3% showed a good response to medical treatment, while only 31.4% of the seronegative patients were classified as good responders (p = 0.01). Thyroid dysfunction was found in 27.4% patients with OMG and the proportion of thyroid dysfunction was not different according to anti-acetylcholine receptor antibody-seropositivity. Seropositivity to acetylcholine receptor antibody is associated with a better response to medical treatment and lower risk of concomitant autoimmune thyroid disease in patients with OMG.

Novel uses of complement inhibitors in myasthenia gravis-Two case reports.

Myasthenia gravis (MG) is a rare, life-threatening immune-related adverse effect (irAE) of immune checkpoint inhibitor (ICI) treatment. C5-complement inhibitors are effective treatments for acetylcholine receptor antibody (AChR ab) positive generalized MG. We describe the use of eculizumab/ravulizumab in two patients with MGreceiving concomitant pembrolizumab. This was a retrospective review of two medical records. Patient 1: An 80-year-old male with recurrent, non-muscle invasive transitional cell carcinoma of the bladder developed ICI-induced AChR ab positive MG (ICI-MG), myositis, and myocarditis 2 weeks after the first dose of pembrolizumab. Myositis responded to corticosteroids. MG responded to eculizumab, followed by ravulizumab. He died of metastatic cancer 8 months later. Patient 2: A 58-year-old male had refractory thymoma-associated AChR ab-positive MG, which responded to eculizumab. He developed metastatic Merkel cell cancer necessitating pembrolizumab. MG remained stable on eculizumab. He had no irAEs for 22 months, with positron emission tomographic resolution of cancer. He then developed mild, indolent retinal vasculitis, which responded to prednisone. Discontinuation of pembrolizumab for 5 months resulted in cancer recurrence; pembrolizumab was resumed with peri-infusion pulse prednisone. MG remained stable and he continues eculizumab. In the first patient, eculizumab, followed by ravulizumab, improved ICI-MG. In the second patient, eculizumab treatment may have had a prophylactic effect on the development of ICI-induced irAEs. The effect of complement inhibition on cancer outcomes of ICI therapy is unknown. A possible biologic basis for complement inhibitors in reducing irAEs of ICI, especially in the presence of underlying autoimmune disease, merits evaluation.

Reduction rate of anti‐acetylcholine receptor antibody titer levels is an early prognostic indicator for myasthenia gravis

AbstractBackgroundA realistic treatment goal for myasthenia gravis (MG) is achieving minimal manifestations or better status with prednisolone at ≤5 mg/day (MM‐or‐better‐5 mg), considering a patient's health‐related quality of life. Prognosis prediction during the early phases of immunotherapies might be critical for determining subsequent treatment strategies; however, the appropriate biomarkers remain unknown.AimThis study aimed to clarify whether the reduction rate of anti‐acetylcholine receptor antibody (RR‐AChR Ab) titer levels is a useful biomarker for predicting MM‐or‐better‐5 mg achievement.MethodsWe retrospectively investigated patients with MG and AChR Abs who received immunotherapy for the first time. The RR‐AChR Ab titer levels were calculated in the early (within 30 days), middle (31–60 days), and late (61–100 days) periods after starting immunotherapies. A receiver operating characteristic (ROC) curve was generated to determine an appropriate cutoff value for RR‐AChR Abs to achieve an MM‐or‐better‐5 mg.ResultsOf 53 patients, 24 (45%) achieved MM‐or‐better‐5 mg after 1 year. For the early period, the RR‐AChR Ab cutoff value to predict MM‐or‐better‐5 mg was 1.68%/day with an area under the curve (AUC) of 0.75 (sensitivity, 85%; specificity, 70%). However, the middle and late posttreatment AUC values did not predict MM‐or‐better‐5 mg achievement.ConclusionThe RR‐AChR Ab might be an appropriate prognostic biomarker during the early period of MM‐or‐better‐5 mg achievement. In the era of early fast‐acting treatment strategies, the RR‐AChR Ab trend after starting immunotherapies may guide the subsequent treatment choices.

Performance evaluation of the EUROIMMUN anti‐acetylcholine receptor enzyme‐linked immunoassay

AbstractObjectivesAnti‐acetylcholine receptor antibodies (AChR Ab) are one of the pathogenic autoantibodies in myasthenia gravis (MG), and they are specifically mentioned in the Japanese clinical guidelines for MG. In the serological diagnosis and measurement of autoantibodies as an adjunct marker for MG, the radioimmunoassay (RIA) method has been conventionally used as the gold standard. However, there have been several worldwide concerns regarding the use of radioisotopes. In this study, we evaluated the performance of the EUROIMMUN AChR Ab enzyme‐linked immunosorbent assay (ELISA) in comparison with RIA.MethodsELISA reproducibility and dilution linearity were analyzed using AChR Ab‐positive samples. Sera from 50 patients with suspected MG and 50 healthy donors were used to assess the correlation and qualitative agreement between the two methods.ResultsThe ELISA showed good interassay precision and dilution linearity. The correlation coefficient, sensitivity, specificity and overall agreement of the ELISA in comparison with the conventional RIA amounted to 0.87, 98%, 92% and 95% (kappa = 0.895), respectively. Analysis of the discordant results suggested that the ELISA might be more capable of detecting low AChR Ab reactivity in patients with suspected MG.ConclusionsThe AchR Ab ELISA provides a reliable tool for the quantification of AchR Ab, supporting the diagnosis of MG. As a non‐isotopic assay with good precision, shorter handling time and high correlation with the conventional RIA, the AChR ELISA could be a useful alternative in the laboratory routine.

Clinical Outcomes in COVID-19 patients with pre-existing myasthenia gravis:

INTRODUCTION: Myasthenia gravis (MG) presents an additional challenge in managing COVID-19 as outcomes potentially depend on prior disease control and treatment. Yet the role of pre-existing MG in COVID-19 outcomes has not been established.&#x0D; METHODS: We searched PubMed, Scopus, and Web of Science databases for reports of MG patients with confirmed COVID-19 until March 2022. We analyzed data on patient demographics, chronicity, and MG control at baseline pre-COVID, treatment history and outcome following COVID infection.&#x0D; RESULTS: Twenty-nine publications with 119 patients (females n=75, age range 20-93 years, AChR Ab positive n= 65, MuSK Ab positive n= 5, seronegative n=14, unknown n=35) were included. Eighty-three (70%) were hospitalized, more than half with MG exacerbation. There was no significant difference in disease duration or control of MG symptoms at baseline between hospitalized and non-hospitalized. Hospitalization was associated with higher dose of daily prednisone but a comparable proportion of patients were on steroid-sparing agents. Among hospitalized patients, 40% were intubated uncorrelated with MG baseline control. Unfavorable outcome was not always associated with MG exacerbation. Amongst those discharged,75% received intravenous immunoglobulin (IVIG) or Plasmapheresis (PLEX) for MG exacerbation as compared to 67% with a fatal outcome didn’t receive either.&#x0D; CONCLUSION: Preexisting MG does not appear to be associated with severe COVID-19 outcomes. Higher dose of prednisone prior to COVID-19 infection is associated with increased risk of hospitalization but MG control at baseline did not determine worse outcome. IVIG/PLEX appears safe and potentially can reduce fatality in patients with COVID-19 experiencing MG exacerbation.

P.042 Could Live Cell-Based Assay increase the acetylcholine receptor autoantibodies seropositivity in patients with clinical suspicion of myasthenia gravis?

Background: AChR antibodies (Abs) in Myasthnia Gravis (MG) are detected in approximately 50% of ocular and 85% of generalized MG by the current gold standard radioimmunoprecipitation assay (RIPA). Recently, fixed and lived Cell-Based assays (L-CBA) are developed. We clinically validated our in-house L-CBA in detecting AChR Ab in clinically suspected MG patients. Methods: Between January 2020 and April 2022, we assayed 10167 sera for AChR Ab by RIPA. We also assayed 4349 of AChR Ab seronegative sera of the above suspected MG samples for anti-MuSK Ab by RIPA. Then 1228 sera of double seronegative and/or borderline AChR Ab was assessed by L-CBA for AChR Ab. For clinical validation, we obtained clinical information on 36 seropositive cases for AChR Ab by L-CBA. Results: We found additional eighty-four cases seropositive for AChR Ab by L-CBA. The clinical information was obtained for 36 cases and based on their final diagnosis, twenty had generalized MG, thirteen had ocular MG, 2 not yet diagnosed and 1 case was of not-MG. Conclusions: The L- CBA has demonstrated improved sensitivity and higher diagnostics performance than RIPA. The L-CBA allowed improved clinical diagnosis and increased seropositivity (by 7%) in clinically suspected MG patients who were earlier seronegative/borderline for AChR Ab by RIPA.

P.040 Long-term efficacy and safety of ravulizumab in adults with anti-acetylcholine receptor antibody-positive generalized myasthenia gravis

Background: The 26-week double-blind, randomized, placebo-controlled period (RCP) of the CHAMPION MG study (NCT03920293) demonstrated ravulizumab’s efficacy and tolerability in anti-acetylcholine receptor antibody-positive (AChR Ab+) generalized myasthenia gravis (gMG). Methods: In the ongoing open-label extension (OLE), patients receive intravenous ravulizumab (blind loading dose in placebo-treated patients or bridging dose in ravulizumab-treated patients, then 3000–3600 mg according to body weight every 8 weeks) for ≤4 years. Data from RCP baseline up to Week 60 were analyzed. Results: Ravulizumab’s long-term efficacy (n=161) and safety (n=169) were assessed. Patients who switched from placebo in the RCP to ravulizumab in the OLE (n=83) showed rapid improvement (least squares mean, 95%CI) in Myasthenia Gravis-Activity of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) total scores, which were maintained through 34 weeks (MG-ADL: −1.7, −2.7 to −0.8; QMG: −3.1, −4.2 to −1.9). Improvements achieved by ravulizumab-treated patients (n=78) in the RCP were sustained through 60 weeks (MG-ADL: −4.0, −4.8 to −3.1; QMG: −4.1, −5.4 to −2.9). Ravulizumab was well tolerated; no meningococcal infections were reported. Four deaths unrelated to study treatment occurred. Conclusions: Ravulizumab demonstrated sustained improvements in MG symptoms and was well tolerated for up to 60 weeks in adults with AChR Ab+ gMG.

Ravulizumab: A Review in Generalised Myasthenia Gravis.

Ravulizumab (ULTOMIRIS®) is the first long-acting complement C5 inhibitor (administered intravenously every 8 weeks) to be approved in several countries globally, for adults with generalised myasthenia gravis (gMG) who are anti-acetylcholine receptor antibody-positive (AChR Ab+). In the phase III CHAMPION MG trial, intravenous ravulizumab was associated with statistically significant improvements in the MG-Activities of Daily Living scale at week 26 of treatment compared with placebo in adults with AChR Ab+ gMG. Improvements in the Quantitative MG scale total score were also statistically significantly higher in ravulizumab than placebo recipients. These improvements were sustained to week 26 of treatment. Ravulizumab was generally well tolerated; the most common treatment-emergent adverse events were headache, diarrhoea and nausea. Efficacy and tolerability data for up to 1 year from the ongoing open-label extension phase are consistent with those from the randomized, placebo-controlled phase; further results are awaited with interest. Thus, ravulizumab is an efficacious, generally well tolerated and convenient treatment option in adults with AChR Ab+ gMG, expanding the options available for gMG management.

Subgroup outcomes from RAISE: A randomized, Phase 3 trial of zilucoplan in generalized myasthenia gravis (P1-5.006)

Subgroup outcomes from RAISE: A randomized, Phase 3 trial of zilucoplan in generalized myasthenia gravis (P1-5.006)

A Phase 3, Open-Label, Multicenter Study To Evaluate Eculizumab In Adolescents With Refractory Generalized Myasthenia Gravis (S5.009)

A Phase 3, Open-Label, Multicenter Study To Evaluate Eculizumab In Adolescents With Refractory Generalized Myasthenia Gravis (S5.009)

Seeing Double: a Case of a Massive Type B2 Thymoma Presenting with Pseudo-Internuclear Ophthalmoplegia (P9-13.004)

<h3>Objective:</h3> NA <h3>Background:</h3> Thymomas are rare, malignant epithelial cell tumors usually diagnosed in the 5th decade. Median tumor size is approximately 5 cm. An estimated 20 – 25% present as paraneoplastic myasthenia gravis (MG) with positive acetylcholine receptor antibodies (AChR Ab). A rarely described presentation of MG is pseudo-internuclear ophthalmoplegia (p-INO). This presents a diagnostic conundrum as INO is discretely localizable to the brainstem and more commonly associated with cerebrovascular disease or demyelination. <h3>Design/Methods:</h3> NA <h3>Results:</h3> A 27-year-old man presented with a three-month history of binocular horizontal diplopia, night sweats, weight loss and generalized weakness. The rapid progression of weakness occurred almost immediately following the COVID-19 vaccine. Examination demonstrated bilateral INO, worrisome for central nervous system inflammatory demyelination. An MRI of brain and cervical spine showed no evidence of demyelination, but the thoracic MRI showed a large soft tissue mass in the right hemithorax. A chest CT demonstrated a massive multilobulated mass encompassing almost the entirety of the right thoracic cavity. Given the mass in conjunction with the neurological symptoms, AchR Ab was obtained demonstrating positivity (51.2 nmol/L) for MG. Biopsy revealed thymoma type B2 and positron emission tomography showed metastatic disease, stage IVa. The patient was treated with four cycles of cisplatin, cyclophosphamide, and doxorubicin with prednisone, as well as a thymus gland resection. He was additionally started on pyridostigmine 60mg every 4 hours which improved his p-INO and generalized weakness. <h3>Conclusions:</h3> This case represents a rare presentation of myasthenia gravis in a young patient with p-INO. The incidental finding of a large thymoma (measuring ~30cm) discovered on thoracic spine imaging for work-up of demyelinating disease prompts alternative diagnostic consideration when presented with MRI-negative INO. It also evokes the question, should there be more emphasis on expediting CT chest imaging to evaluate for thymoma in patients with antibody positive MG. <b>Disclosure:</b> Dr. Hart has nothing to disclose. Maja Ostojic has nothing to disclose. Dr. Farrell has nothing to disclose. Dr. Esch has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen.

Achievement of Improved Post-Intervention Status in Patients with Generalized Myasthenia Gravis Treated with Ravulizumab during the CHAMPION MG Study (S5.008)

Achievement of Improved Post-Intervention Status in Patients with Generalized Myasthenia Gravis Treated with Ravulizumab during the CHAMPION MG Study (S5.008)

Ravulizumab pharmacokinetics and pharmacodynamics in patients with generalized myasthenia gravis

IntroductionThe terminal complement C5 inhibitor ravulizumab has a long elimination half-life, allowing maintenance dosing every 8 weeks. In the 26-week, double-blind, randomized, placebo-controlled period (RCP) of the CHAMPION MG study, ravulizumab provided rapid and sustained efficacy and was well tolerated in adults with anti-acetylcholine receptor antibody-positive (AChR Ab+) generalized myasthenia gravis (gMG). This analysis evaluated the pharmacokinetics (PK), pharmacodynamics (PD), and potential immunogenicity of ravulizumab in adults with AChR Ab+ gMG.MethodsData were analyzed from 86 patients who received ravulizumab in the CHAMPION MG RCP. Ravulizumab dosing was weight-based: initial loading dose of 2400/2700/3000 mg on Day 1 and maintenance doses of 3000/3300/3600 mg on Day 15 and then every 8 weeks. PK parameters were estimated from serum ravulizumab concentrations determined pre- and post-dose; PD effects of ravulizumab on serum free C5 concentrations were measured; and immunogenicity was assessed using anti-drug antibody and neutralizing-antibody assays.ResultsTarget serum ravulizumab concentrations (> 175 µg/mL) were achieved immediately after the first ravulizumab dose (within 30 min of infusion completion) and maintained throughout the 26-week treatment period irrespective of patient body weight. Following the final maintenance dose, mean Cmax was 1548 µg/mL and Ctrough 587 µg/mL; no meaningful differences were noted among body-weight categories. Inhibition of serum free C5 was immediate, complete (< 0.5 μg/mL), and sustained throughout treatment in all patients. No treatment-emergent anti-drug antibodies were observed.ConclusionsPK/PD evidence supports the use of ravulizumab every 8 weeks for immediate, complete, and sustained inhibition of terminal complement C5 in adults with AChR Ab+ gMG.Trial registrationClinicalTrials.gov ID: NCT03920293 (April 18, 2019).

Ophthalmologic clinical features of ocular myasthenia gravis.

To investigate the clinical features of ocular myasthenia gravis (OMG) in ophthalmology. A total of 28 patients with ptosis or diplopia who were followed for at least 6 months between March 2016 and February 2022 were included in this study. The clinical symptoms of the patients and test results were analyzed. According to the positivity of serologic or electrophysiologic test, these patients were divided into 2 groups (positive and negative OMG results) and according to the clinical symptoms of diplopia or ptosis for comparison. Ptosis, diplopia, and both ptosis and diplopia were present in 6 (21.43%), 14 (50.0%), and 8 (28.57%) patients, respectively. Acetylcholine receptor auto-antibody (AchR Ab) was positive in 16 (57.14%) of 28 patients and the ice test was positive in 13 (92.86%) of 14 patients with ptosis. Abnormal thymic lesions were presented in 7 (25.0%) patients, and a definite improvement in response to pyridostigmine was observed in 27 (100.0%) patients. Both ptosis and diplopia were significantly higher in the group with positive results than that in the negative results group (P = .025). In addition, both horizontal and vertical diplopia was significantly higher in the group with AchR Ab titer > 5.0 than that in the group with AchR Ab titer < 5.0 (P = .041). After excluding cranial nerve palsy, if there is ptosis and diplopia, especially vertical diplopia, the possibility of OMG should be considered.

Prognostic predictors of remission in ocular myasthenia gravis.

Ocular myasthenia gravis (OMG) constitutes 15% of all myasthenia gravis patients. One hundred eight patients with OMG followed-up for over 36months were retrospectively evaluated regarding factors associated with remission. Demographic features, neuro-ophthalmologic findings at onset, acetylcholine receptor (AChR Ab) and muscle-specifc tyrosine kinase antibodies (MuSK Ab), thymic status, single fiber electromyography (SFEMG) results were the variables considered. Median age of disease onset was 57years (range 18-82years). Clinical features at onset was isolated ptosis in 55 (50.9%) and isolated diplopia in 33 (30.6%) patients. Combined ptosis and diplopia were present in 20 (18.5%) patients. Among 75 patients with ptosis, it was unilateral in 65 (86.7%) and bilateral in 10 (13.3%). AChR Abs were found in 66 (61.1%) and MuSK Abs in 2 (1.9%) patients. SFEMG abnormality was detected in 74 (68.5%) patients. Thymoma was present in 16 (14.8%) and thymic hyperplasia in 6 (5.6%) patients. Forty-one patients (37.9%) had been treated with pyridostigmine alone. Sixty-seven (62%) patients were given immunosupressive drugs. In 53 (49.1%) prednisone was used and in 14 (12.9%) patients it was combined with azathioprine. Thymectomy was performed in all 16 patients with thymoma. Complete stable remission (CSR) was achieved in 49 (45.4%) patients. Fifty-nine (54.6%) patients had reached minimal manifestation (MM) status; 32 (29.6%) having a status of MM-1 and 27 (25%) a status of MM-3. The presence of AchR Abs (p = 0.034) and an abnormal SFEMG (p = 0.006) at onset as increased risk factors for the presence of ongoing signs necessitating medical treatment.

Safety and effectiveness of eculizumab in Japanese patients with generalized myasthenia gravis: Analysis of 1‐year postmarketing surveillance

AbstractIntroductionEculizumab, a terminal complement protein C5 inhibitor, is approved in Japan for the treatment of patients with anti‐acetylcholine receptor antibody‐positive (AChR Ab+) generalized myasthenia gravis (gMG) that is difficult to control with plasmapheresis or high‐dose intravenous immunoglobulin therapy.MethodsThis analysis of mandatory postmarketing surveillance in Japan assessed the safety and effectiveness of eculizumab in patients with AChR Ab+ gMG who had completed case‐report forms at 26 wk after eculizumab initiation up to the cutoff date of April 2021. Changes from baseline were assessed for Myasthenia Gravis‐Activities of Daily Living (MG‐ADL) and Quantitative Myasthenia Gravis (QMG) total scores overall, and MG‐ADL scores in patient subgroups according to sex, age at diagnosis and baseline, and baseline disease severity. The change in concomitant corticosteroid use was also evaluated.ResultsData were available for 134 adults (67.2% female; mean age 51.9 y); the effectiveness‐analysis set comprised 126 patients. After 26 wk, 78% of patients were continuing eculizumab treatment. Adverse drug reactions were reported by 49 patients (37%) (most frequently headache [n = 10]). Improvements in MG‐ADL scores were seen regardless of sex; age at diagnosis (&lt;50/≥50 y); baseline age (18 to &lt;40/≥40 to &lt;65/≥65 y); Myasthenia Gravis Foundation of America disease classification (IIa/IIb/IIIa/IIIb/IVa/IVb/V); or baseline MG‐ADL score (&lt;6/≥6). Of patients receiving corticosteroids, the proportion receiving low doses (average ≤5 mg/d) increased from 7.0% before eculizumab initiation to 26.4% by Week 52.ConclusionEculizumab was well tolerated and effective in treating AChR Ab+ gMG across a broad spectrum of adult Japanese patients with difficult‐to‐control gMG.

The clinical utility of comprehensive measurement of autoimmune disease-related antibodies in patients with advanced solid tumors receiving immune checkpoint inhibitors: a retrospective study

BackgroundThe comprehensive measurement of autoimmune disease-related antibodies (Abs) before immune checkpoint inhibitor (ICI) treatment may be useful for predicting the development of immune-related adverse events (irAEs); however, the clinical utility is not well known.Materials and methodsWe retrospectively analyzed patients with advanced solid tumors treated with ICI monotherapy or doublet combination therapy between July 2014 and December 2020 at single institute. Anti-nuclear antibody (ANA), anti-thyroglobulin (Tg) Ab, anti-thyroid peroxidase (TPO) Ab, anti-glutamic acid decarboxylase (GAD) Ab, anti-acetylcholine esterase receptor (AchR) Ab, and platelet-associated immunoglobulin G (PA-IgG) Ab were comprehensively measured for the screening before ICI therapy.ResultsOf 275 registered patients (median age, 70 years; male, 64.4%; Eastern Cooperative Oncology Group performance status of 0 or 1, 88.7%; and prior regimen of 0-1/≥2, 88.7%/11.3%), 128 non-small-cell lung cancer, 35 gastric cancer, 33 head and neck cancer, 24 melanoma, 19 renal cell carcinoma, 13 urothelial carcinoma, 12 esophageal cancer, 5 malignant mesothelioma of pleura, 2 endometrial cancer, and 4 other cancer were included. The number of patients with positive ANA, Tg, TPO, PA-IgG, GAD, and AchR Abs was 52 (24.9%), 38 (14.5%), 11 (10.1%), 6 (3.5%), 5 (2.0%), and 1 (0.5%), respectively. There was no association between the development of any irAEs and Abs positivity, while thyroid dysfunction developed more frequently among patients with than without Tg Ab or TPO Ab (39.5% versus 12.5%, P < 0.01; 45.5% versus 14.3%, P = 0.02).ConclusionsThe clinical utility of comprehensive measurement of autoimmune disease-related Abs before introduction of ICI therapy was limited for predicting irAE. However, Tg and TPO Abs were risk factors as regards the development of ICI-induced thyroid dysfunction.

Effects of rituximab on prognosis in myasthenia gravis: A single-center experience from Turkey

Management of treatment-resistant patients with myasthenia gravis (MG) remains an important issue. This study aimed to evaluate the effects of rituximab (RTX) treatment on the prognosis of patients with acetylcholine receptor autoantibody-positive (AChR-Ab+), muscle-specific kinase autoantibody-positive (MuSK-Ab+), or seronegative or double seropositive MG. Nineteen patients treated with RTX between 2015 and 2020 were included in this study. Demographic and clinical characteristics, prognosis, and prognostic predictors of MG were evaluated retrospectively. The Myas-thenia Gravis Foundation of America Post-Inter-vention Status (MGFA-PIS) before RTX treatment (pre-RTX) and after RTX treatment (post-RTX) were recorded. A total of 10 patients (52.6%) were AchR Ab+, 6 patients (31.6%) were MuSK Ab+, 1 patient (5.3%) was seronegative, and 2 patients (10.5%) were double seropositive. Steroid dose was pre-RTX 38.9±5.7 (25-45), it was post-RTX 10.5±10.3 (0-30) (p<0.001). Post-RTX steroid treatment was discontinued in 6 of 19 patients (p=0.041). Only three patients received intravenous immunoglobulin at the post-RTX follow-up (p<0.001). In post-RTX 12th month, the MGFA-PIS score was as minimally manifestation or better in 9 patients (47.3%) and improved or was better in 18 patients (94.7%) (p-value 0.004; <0.001, respectively). The improvement in MGFA-PIS scores post-RTX was similar in MuSK-Ab+ and AChR-Ab+ patients. The data are insufficient in seronegative and double seropositive patients and RTX must be considered in the treatment of suitable patients with MuSK-Ab+ and AChR-Ab+ refractory MG.

To measure musk ABS in ACHR AB negative sera: RIPA is more specific, and SPR is more sensitive

Muscle-specific kinase (MuSK) myasthenia gravis (MG) is often a more severe form of MG that presents with a rapid onset and prominent bulbar symptoms. Today, the diagnosis of MuSK MG is heavily reliant on the antibody (Ab) status of the patient. In most laboratories worldwide, the Abs are measured by radio immune precipitation assay (RIPA). We have developed another testing platform using surface plasmon resonance (SPR) technology. Our aim was to measure the clinical sensitivity and specificity for two different MuSK Ab assays.