Non-steroidal Immunosuppressants Research Articles

Risk factors of Carbapenem-resistant Enterobacterales intestinal colonization for subsequent infections in hematological patients: a retrospective case-control study.

Infections caused by Carbapenem-resistant Enterobacterales (CRE) have high treatment costs, high mortality and few effective therapeutic agents. This study aimed to determine the risk factors for progression from intestinal colonization to infection in hematological patients and the risk factors for 30-day mortality in infected patients. A retrospective case-control study was conducted in the Department of Hematology at Shandong Provincial Hospital affiliated to Shandong First Medical University from April 2018 to April 2022. Patients who developed subsequent infections were identified as the case group by electronic medical record query of patients with a positive rectal screen for CRE colonization, and patients who did not develop subsequent infections were identified as the control group by stratified random sampling. Univariate analysis and logistic regression analysis determined risk factors for developing CRE infection and risk factors for mortality in CRE-infected patients. Eleven hematological patients in the study developed subsequent infections. The overall 30-day mortality rate for the 44 hematological patients in the case-control study was 11.4% (5/44). Mortality was higher in the case group than in the control group (36.5 vs. 3.0%, P = 0.0026), and septic shock was an independent risk factor for death (P = 0.024). Univariate analysis showed that risk factors for developing infections were non-steroidal immunosuppressants, serum albumin levels, and days of hospitalization. In multivariable logistic regression analysis, immunosuppressants [odds ratio (OR), 19.132; 95% confidence interval (CI), 1.349-271.420; P = 0.029] and serum albumin levels (OR, 0.817; 95% CI, 0.668-0.999; P = 0.049) were independent risk factors for developing infections. Our findings suggest that septic shock increases mortality in CRE-infected hematological patients. Hematological patients with CRE colonization using immunosuppressive agents and reduced serum albumin are more likely to progress to CRE infection. This study may help clinicians prevent the onset of infection early and take measures to reduce mortality rates.

Efgartigimod Alfa (Vyvgart)


 CADTH recommends that Vyvgart be reimbursed by public drug plans for the treatment of adult patients with generalized myasthenia gravis (gMG) if certain conditions are met.
 Vyvgart should only be covered to treat patients who have a diagnosis of class II to IV gMG based on the Myasthenia Gravis Foundation of America (MGFA) system, tested positive for anti–acetylcholine receptor (AChR) antibodies, and have a Myasthenia Gravis Activities of Daily Living (MG-ADL) scale score of at least 5. Vyvgart should only be covered to treat patients if their symptoms persist despite a stable dose of conventional therapy with acetylcholinesterase inhibitors (AChEIs), corticosteroids (CSs), and/or nonsteroidal immunosuppressants (NSISTs).
 Vyvgart should not be reimbursed when given during a gMG exacerbation (i.e., moment when patient experience weakness in some or all muscles, without needing assistance to breath) or crisis (i.e., moment when respiratory muscles are too weak, limiting air flow in and out of lungs, and as a result, patient is unable to breathe), or within 3 months of thymectomy (i.e., surgical removal of thymus gland). Vyvgart should only be reimbursed if prescribed by or in consultation with a neurologist with expertise in managing patients with gMG, and the cost of Vyvgart is reduced. Vyvgart should not be used concomitantly with rituximab or complement inhibitors.

Cardiac Sarcoidosis treated with non-steroidal immunosuppressive therapy

Abstract Background Non-steroidal immunosuppressive therapy is a potential treatment strategy for cardiac sarcoidosis. However, due to the lack of robust evidence, it is not recommended as an established treatment option in the guideline. Purpose The purpose of the study is to demonstrate the clinical outcome of the patients with cardiac sarcoidosis using non-steroidal immunosuppressive therapy in a retrospective registry entitled ILLUMINATE-CS (ILLUstration of the Management and prognosIs of JapaNese pATiEnts with Cardiac Sarcoidosis). Methods Of an entire cohort of 512 patients, 26 who received immunosuppressive therapy other than steroids were recruited for the analysis. The clinical outcome included all-cause death, fatal ventricular arrhythmic event (FVAE), and worsening heart failure with hospitalization. Results The reasons to use non-steroidal immunosuppressant were increased fluorodeoxyglucose (FDG) accumulation on the heart suggesting worsened inflammation (n = 13), side effects of steroid (n = 7), ventricular tachycardia or frequent ventricular premature contraction (n=4), complete atrioventricular block (n = 2), worsened symptom relating to non-cardiac sarcoidosis including neuro and pulmonary sarcoidosis (n = 2), and the other reason (n = 2), with some overlapping. Used non-steroidal immunosuppressants were comprised of methotrexate (n = 20, 6.9 ± 2.1 mg/week), cyclosporine (n =2, 75 or 100 mg/day), cyclophosphamide (n = 2, 25 or 50 mg/day), and azathioprine (n = 3, 100 mg/day in each). Side effects of non-steroidal immunosuppressant were observed in six cases and included one with methotrexate-related interstitial pneumonia, one with a methotrexate-associated lymphoproliferative disorder, one with septic coxitis with methotrexate, one with methotrexate-induced acute kidney injury, one with methotrexate-induced hepatic dysfunction, and one with azathioprine-induced anemia. After the addition of a non-steroidal immunosuppressant, steroids could be reduced in 14 cases of 26 cases with a median maintenance dose of 5 (interquartile range of 5–17) mg, although no cases stopped steroids. Of 13 cases who started non-steroidal immunosuppressant for the increased FDG uptake, decreased FDG uptake was observed in seven cases at the follow-up scan. Clinical outcome events were observed in 11 cases (42.3%). Detected events included all-cause death in five cases (19.2%), FVAE in four cases (15.4%), and worsening heart failure with hospitalization in five cases (19.2%), with some overlapping. Conclusions Non-steroidal immunosuppressive therapy may be a possible treatment option for patients who are not stabilized using sole steroid therapy or who suffer from the side effects of steroids.

Current drug treatment of myasthenia gravis.

Myasthenia Gravis (MG) is a rare neurological disorder affecting the neuromuscular junction. Clinical hallmarks are fatigability and weakness affecting the extraocular, axial, limb and/or respiratory muscles. Despite immunosuppressive treatment, mainly based on corticosteroids and nonsteroidal immunosuppressants, the burden of MG is still significant, both in terms of inadequate disease control and burdensome side effects. Driven by such limits, the past years have been characterized by an escalation of MG drug development, with novel molecules which now focuses on having a more targeted effect, with a higher safety and efficacy profile. As the pathogenic mechanism of MG are slowly being unravelled, new potential targets for treatments are being considered. This has led since 2017 to the Food and Drug Administration (FDA)-approval of three new drugs that either act by blocking the complement system (i.e., eculizumab and ravulizumab) or by blocking the neonatal Fc receptor thus preventing immunoglobulin recycling and reducing imunoglobulin G (IgG) antibodies (i.e., efgartigimod). Other drugs, with similar mechanism of action, are currently under review for approval. The repertoire of available and developmental therapies for MG is rapidly expanding, finally responding to the unmet need of a more targeted and effective therapeutic approach in MG.

Tofacitinib therapy in refractory inflammatory myositis: a retrospective cohort study of 41 patients.

To evaluate the efficacy and safety of tofacitinib in treatment-refractory inflammatory myositis in a real-world clinical setting. All patients with refractory inflammatory myositis treated with tofacitinib from a single urban centre in Vancouver, British Columbia, Canada, were included from June 2016 to December 2022. The medical records of these patients were retrospectively reviewed. A total of 41 patients were included, 23 with classic DM, 12 with amyopathic DM (ADM) and six with PM phenotype. The patients failed an average of four to five non-steroidal immunosuppressants before initiation of tofacitinib. In the classic DM and ADM group, tofacitinib offered clinically and statistically significant cutaneous improvement. In all myositis patients including the PM phenotype, no meaningful muscle strength response to tofacitinib was observed. 53.7% of the patients discontinued tofacitinib due to lack of benefit or death. Of the 19 patients who remained on tofacitinib at the conclusion of this study, tofacitinib demonstrated clinically and statistically significant improvement in cutaneous disease activity. Tofacitinib appears to be highly effective in targeting cutaneous manifestations in classic DM and ADM; however, minimal benefit in muscle strength in the DM or PM phenotype were observed.

#3081 ASSOCIATION OF URINE PROTEIN EXCRETION LEVELS, AS A MEASURE OF DISEASE ACTIVITY, AND QUALITY OF LIFE IN IGA NEPHROPATHY PATIENTS

Abstract Background and Aims Little is known about the quality of life (QoL) of patients with IgA nephropathy (IgAN). Understanding the relationship between disease activity (as measured by urine protein excretion [UPE]) and QoL could allow decision-makers to understand how treatments that improve UPE might improve patient QoL. Methods The 2021 United States subset of the Adelphi IgAN Disease Specific Programme™ was a point-in-time survey of 43 nephrologists (who completed structured forms for 305 IgAN patients) and 70 patients (who elected to complete patient surveys of the 305). This analysis utilised physician-reported data (patient demographics, disease characteristics, and current 24-hour UPE levels [categories: ≤0.5, >0.5 to ≤1, >1 to ≤2, >2 to ≤3.5, >3.5 grams/day]) and patient-reported data (symptoms, Kidney Disease Quality of Life [KDQOL] scores, and EQ-5D scores). The association between UPE and patient-reported symptoms was evaluated using chi-squared and Fisher's exact tests. The association between UPE and QoL (KDQOL, EQ-5D) was evaluated using generalized linear regression to adjust for age, sex, chronic kidney disease stage, corticosteroid use, and non-steroidal immunosuppressant use. Results The analytical dataset included 69 patients with UPE data (reported by 8 physicians) out of the 70 patients who completed the patient survey. Of these 69, data were complete for the symptoms (n=63), KDQOL (n=60), and EQ-5D (n=67). Patients were an average age of 43 years, an average BMI of 26.3, 49% male, 55% White, 23% Asian, 64% never smokers, 78% in full-time occupation, and 74% with commercial health insurance. The most prevalent comorbidities were hypertension (33%), hyperlipidemia (30%), and diabetes (11%). UPE was not associated with any demographic characteristics, regular dialysis, or kidney transplants. Among comorbidities, higher UPE was associated with a higher percentage of hyperlipidaemia (P = .03). Among medications for IgAN, higher UPE was associated with a higher percent use of diuretics (P = .046), sodium-glucose co-transporter 2 inhibitors (P = .002), corticosteroids (P = .0009), non-steroidal immunosuppressants (p<0.0001), and anti-depressants (P = .0009). Higher UPE was associated with a higher percentage of patient-reported aching joints (P = .04), self-awareness of high cholesterol (P = .001), tiredness (P = .005), swollen feet/ankles/legs (p<0.0001), sleep problems (P = .02), feeling sick (P = .0003), and tea-colored urine (P = .03). Higher UPE was associated with worse KDQOL scores (burden [p<0.0001], effects [P = .007], physical health [P = .002], and mental health [p<0.0001]). After adjustment (Table 1), higher UPE continued to be associated with worse KDQOL burden (P = .01) and mental health (P = .03) scores. Unadjusted and adjusted analyses (Table 2) indicated that higher UPE was associated with worse EQ-5D scores. Conclusion The results indicate that higher levels of disease activity (UPE) in IgAN are associated with increased symptom burden, worse kidney disease QoL, and worse overall QoL.

Real world study on prevalence, treatment and economic burden of myasthenia gravis in Italy

The purpose of this study was to investigate the epidemiology, management, and economic burden of myasthenia gravis in settings of real clinical practice. The analysis used administrative databases covering around 12 million subjects across Italy and included all adult patients with hospitalization discharge diagnosis or active exemption code for myasthenia gravis or with ≥1 pyridostigmine prescription from 2011 to 2018. The estimated prevalence of myasthenia gravis during 2018 was in the range 13.5–29.3/100,000 people (depending on the criteria applied), corresponding to 8190–17,728 alive patients, when reproportioning data to the entire Italian population. Overall 4397 patients with myasthenia gravis (mean age 61.7 years, 46.6% males) were included. A large pyridostigmine use was observed (84.0%–46.8% from 1st to 3rd year of follow-up), followed by corticosteroids (54.5%–44.6% from 1st to 3rd year of follow-up) and non-steroidal immunosuppressants (16% over follow-up). Total direct healthcare costs for myasthenia gravis were 4-times higher than those of the general population (€3771 and €869, respectively), and up to 9-fold increased when considering patients with exacerbation (€7827). These findings showed the epidemiologic burden of myasthenia gravis and the complexity of the therapeutic management for the affected patients, with large use of treatments and elevated healthcare expenditures.

Erosive and ulcerative stomatitis in dogs and cats: which immune-mediated diseases to consider?

Immune-mediated and autoimmune diseases of the skin often present with oral cavity involvement. Autoimmune subepidermal blistering diseases and pemphigus vulgaris are classic examples. While the primary lesions (vesicles and bullae) are relatively specific, these fragile lesions evolve rapidly into erosions and ulcers, which are lesion types that overlap with many diseases. Furthermore, some immune-mediated diseases such as severe adverse drug reactions, lupus diseases, canine uveodermatological syndrome, and vasculitis, may or may not involve the oral cavity, and often nonoral clinical manifestations are more diagnostic. In these situations, disease knowledge combined with signalment, lesion distribution, and history help to narrow the differentials. Surgical biopsy is required for confirmation in most diseases, while immunosuppressive treatments most typically involve glucocorticoids with or without nonsteroidal immunosuppressants.

Ravulizumab for the treatment of myasthenia gravis

Introduction Myasthenia gravis (MG) is a neurological B-cell mediated autoimmune disorder affecting the neuromuscular junction. MG therapeutics have always relied on non-selective immunosuppression with oral steroids and non-steroidal immunosuppressants, mainly with good clinical response. However, clinical stabilization is often reached at the cost of many troublesome side effects and up to 15% of MG patients are deemed as refractory to conventional immunosuppression. This highlights the need of a more targeted and efficacious therapeutic approach. Results from the randomized-controlled period of the CHAMPION study demonstrate a good safety, tolerability, and efficacy profile of ravulizumab compared to placebo. Like eculizumab, ravulizumab is an anti-C5 monoclonal antibody, but with an enhanced pharmacokinetic profile, that allows dosing every 8 weeks. Areas covered We provide an overview of ravulizumab biological features and results from the phase III CHAMPION MG (NCT03920293) study. Expert opinion Data of the CHAMPION MG trial demonstrate that ravulizumab is effective and safe in the treatment of generalized MG. Having a rapid clinical effect, with long-term clinical response, ravulizumab could represent a selective immunosuppressive drug of choice in the future therapeutic algorithm of MG, where conventional immunosuppressants slowly leave room for newer drugs with a more targeted mechanism of action.

331 Prior treatment usage in patients with atopic dermatitis initiating dupilumab: an update from the GLOBOSTAD registry

Abstract The efficacy and safety of dupilumab have been reported previously based on data from controlled clinical trials. The GLOBOSTAD study extends the scope of these trials by providing real-world data. This analysis reports prior treatment usage in patients with atopic dermatitis (AD) initiating treatment with dupilumab in a real-world setting. This 5-year, international, multicentre, non-interventional study (GLOBOSTAD; NCT03992417) included patients ≥12 years-old with moderate-to-severe AD (Investigator’s Global Assessment score ≥3) who initiated dupilumab treatment based on country-specific prescribing information. Data reported are for the population at baseline (N = 952, data cut-off: March 2022). At the study entry, the mean (standard deviation) Patient-Oriented Eczema Measure (POEM) score was 19.7 (6.4). POEM range is 0–28 and scores greater than 17 are consistent with severe or very severe disease. The mean (standard deviation) pruritus on the 0–10 Numerical Rating Scale (NRS) at study entry was 6.3 (2.1). Patient use of systemic treatments such as non-steroidal immunosuppressants (32.6%) and systemic corticosteroids (17.8%), as well as non-systemic treatments such as topical corticosteroids (47.2%) and calcineurin inhibitors (14.8%) in the 12 months preceding enrolment were reported. Ultraviolet phototherapy in the past 12 months was reported for 3.4% of patients. Patient-reported outcomes, including POEM and pruritus NRS, indicate a considerable burden of disease in patients with AD initiating dupilumab in the real world. A large proportion of patients from GLOBOSTAD reported the use of AD-specific systemic and non-systemic therapies prior to dupilumab initiation.

A real-world analysis of factors associated with high healthcare resource utilization and costs in patients with myasthenia gravis receiving second-line treatment

Despite current treatments, patients with myasthenia gravis (MG) experience unpredictable and inadequately controlled symptoms, lending to variability in the clinical and economic burden of disease. However, limited data are available on MG healthcare costs, and specifically, no data on patients initiating second-line therapy. Using claims data from the IBM® MarketScan® database, we assessed patient characteristics, healthcare resource utilization, and costs among MG patients initiating second-line therapy, and identified potential factors associated with high healthcare costs over a two-year follow-up period. We identified 1498 patients, of whom 49% and 31% received chronic steroids and non-steroidal immunosuppressants (NSISTs) as their second-line therapy, respectively. During follow-up, 49% experienced ≥1 MG exacerbation. Among all patients, mean all-cause total healthcare cost was $106,821 per patient during follow-up, with $88,040 and $18,780 attributed to medical and pharmacy costs, respectively. In a multivariable analysis, variables significantly associated with high cost included use of high-dose steroids, chronic intravenous immunoglobulin (IVIg, ≥6 cycles), and 1 and ≥ 4 (but not 2–3) MG exacerbations in the first year after second-line therapy initiation. Any number of exacerbations were associated with high cost in a univariable analysis. A stratified cost analysis showed that patients with >1 exacerbation, ≥1 treatment switch, and high-dose steroid use in this first year experienced $198,487, $114,037, and $79,752 mean MG-related total healthcare spend during follow-up, respectively. These data suggest that patients receiving chronic IVIg or NSISTs for MG experience significant economic burden. Disease characteristics including exacerbation and treatment history may be an indicator of future high costs.

RWD137 Changing Priorities Among Physician Reported Reasons for Choice of Pharmacological gMG Treatments Across 5 European Countries

Generalized Myasthenia Gravis (gMG) is a chronic, autoantibody condition causing muscle weakness. There is no cure, however a range of pharmacological treatments are currently prescribed, typically acetylcholinesterase inhibitors (AChEIs), corticosteroids, and non-steroidal immunosuppressants (NS-ISTs).

P81: Efficacy of abrocitinib vs. dupilumab in adults with moderate‐to‐severe atopic dermatitis who had an inadequate response or intolerance to nonsteroidal immunosuppressants: results from JADE DARE

P81: Efficacy of abrocitinib vs. dupilumab in adults with moderate‐to‐severe atopic dermatitis who had an inadequate response or intolerance to nonsteroidal immunosuppressants: results from JADE DARE

Comparative-effectiveness research of COVID-19 treatment: a rapid scoping review

ObjectivesThe COVID-19 pandemic has stimulated growing research on treatment options. We aim to provide an overview of the characteristics of studies evaluating COVID-19 treatment.DesignRapid scoping reviewData sourcesMedline, Embase and biorxiv/medrxiv...

Association of immunosuppression treatment with generalization among patients with ocular myasthenia gravis: Apropensity score analysis.

To analyze disease generalization in patients with ocular myasthenia gravis (OMG) treated with immunosuppression compared with patients without immunosuppression treatment. In this retrospective cohort study, we analyzed data from patients with OMG at seven medical centers in China from January 1, 2015 to May 1, 2019 and compared disease generalization in patients (treated with immunosuppression vs. not treated) within 2years of disease onset using raw and inverse probability of treatment weighting (IPTW) analyses. In the study population of 813 patients with OMG, 425 (52.3%) with immunosuppression had a mean (SD) onset age of 50.0 (15.1) years, and 188 (44.2%) were women. The remaining 388 (47.7%) patients were not immunosuppressed (mean age, 48.4 [15.0] years; 185 [47.7%] women). Disease generalization developed in 122 (31.4%) and 37 (8.7%) patients in the non-immunosuppression and immunosuppression groups, respectively. Relative to non-immunosuppression, immunosuppression was associated with a lower risk of generalization in a multivariable-adjusted Cox model (hazard ratio [HR] 0.27; 95% confidence interval [CI] 0.18-0.40; p<0.001) and IPTW-weighted Cox model (HR 0.28; 95% CI 0.19-0.42; p<0.001). In sensitivity analyses, longer duration of immunosuppression was associated with a lower risk of generalization (HR 0.90 for every 1-month increase; 95% CI 0.87-0.92; p<0.001; IPTW-adjusted). Combination therapy with steroids and non-steroidal immunosuppressants showed superior efficacy in reducing the risk of generalization (HR 0.14; 95% CI 0.07-0.26; p<0.001). Immunosuppression significantly reduced the 2-year risk of generalization in patients with OMG.

Dupilumab in Adults with Moderate-to-Severe Atopic Dermatitis and Prior Use of Systemic Non-Steroidal Immunosuppressants: Analysis of Four Phase3 Trials.

IntroductionDupilumab is approved as first-line systemic treatment for adults/adolescents with moderate-to-severe atopic dermatitis (AD) in Europe and elsewhere owing to its favourable benefit–risk profile. However, systemic non-steroidal immunosuppressants (NSISS) are often used as first-line therapy in clinical practice. Impact of prior therapy with NSISS on dupilumab’s treatment effect vs. control has not been described previously. This study assessed dupilumab’s efficacy vs. control in patients with moderate-to-severe AD, comparing treatment effect in patients with/without prior systemic NSISS therapy, in four phase 3 trials.MethodsThis post hoc analysis included 1553 patients randomized to placebo or dupilumab (300 mg q2w) as monotherapy for 16 weeks, or with concomitant topical corticosteroids (TCS) for 16/52 weeks, from four randomized, double-blind, placebo-controlled, phase 3 trials. Patients were stratified by prior use of systemic NSISS and dupilumab-treated patients were analysed against control groups (treated with placebo or placebo + TCS).ResultsDupilumab-treated patients, regardless of prior treatment with NSISS, achieved a significantly higher percentage reduction from baseline in Eczema Area and Severity Index (EASI), SCORing Atopic Dermatitis (SCORAD), Dermatology life Quality Index (DLQI), and Patient-Oriented Eczema Measure (POEM) vs. control; significantly more achieved EASI score ≤ 7, Peak Pruritus Numerical Rating Scale ≤ 4, POEM ≤ 7, and DLQI ≤ 5 by week 4. These rapid, significant improvements were seen with or without concomitant TCS and sustained through end-of-treatment.ConclusionsDupilumab treatment (monotherapy or + TCS) provides rapid, significant, sustained improvements in signs, symptoms, and quality of life in patients with moderate-to-severe AD compared with control, regardless of prior systemic NSISS use.Clinical Trial RegistrationLIBERTY AD SOLO 1: ClinicalTrials.gov identifier NCT02277743, EudraCT 2014-001198-15. LIBERTY AD SOLO 2: ClinicalTrials.gov identifier NCT02277769, EudraCT 2014-002619-40. LIBERTY AD CHRONOS: ClinicalTrials.gov identifier NCT02260986, EudraCT 2013-003254-24. LIBERTY AD CAFÉ: ClinicalTrials.gov identifier NCT02755649, EudraCT 2015-002653-35.Graphic Supplementary InformationThe online version contains supplementary material available at 10.1007/s13555-021-00558-0.

Precise, simplified diagnostic criteria and optimised management of initial-onset Vogt-Koyanagi-Harada disease: an updated review.

Vogt-Koyanagi-Harada (VKH) disease is a primary autoimmune stromal choroiditis. This review aimed to provide a novel perspective of the disease. We took into account recent developments in the understanding of the disease and crucial progress in investigational modalities of the choroid, which has led to new, simpler diagnostic criteria. We analysed recent novel notions in the literature and new diagnostic tools for VKH. We identified the following updates for VKH disease: (1) A crucial differentiation between the acute initial-onset and the chronic forms of the disease; (2) the integration of new, precise imaging methods to assess choroidal inflammation; (3) the promotion of simplified, more reliable diagnostic criteria for acute initial-onset of the disease, based on the sine qua non presence of diffuse choroiditis, detected with indocyanine green angiography (ICGA) and/or Enhanced Depth Imaging OCT (EDI-OCT); and (4) treatment optimisation through early, vigorous, sustained corticosteroid and nonsteroidal immunosuppression, as the first line of treatment for initial-onset VKH disease, and monitoring subclinical choroidal inflammation during follow-ups. Several studies have shown that most patients could discontinue treatment without an inflammation relapse. ICGA and EDI-OCT represented the methods of choice for precisely monitoring disease evolution. Simplified, precise, new diagnostic criteria allow early diagnosis of VKH. In VKH disease, inflammation exclusively originates in the choroidal stroma. Therefore, in many cases, early, sustained treatment, with dual corticosteroid and nonsteroidal immunosuppressive therapy can result in full "healing", which obviates chronic, uncontrolled, subclinical choroidal inflammation.

No correlation between acetylcholine receptor antibody concentration and individual clinical symptoms of myasthenia gravis: A systematic retrospective study involving 67 patients.

ObjectiveTo investigate the correlation between acetylcholine receptor antibodies (AChR‐Ab) concentration levels and individualized clinical symptoms in patients with AChR myasthenia gravis (AChR‐MG) in China.MethodsELISA was used to determine the concentration of AChR‐Ab in patients with MG. The Myasthenia Gravis Foundation of America (MGFA) Clinical Classification, Quantitative Myasthenia Gravis (QMG) score, and MG‐specific activities of daily living (MG‐ADL) scoring systems were used to evaluate the clinical status of patients. Spearman correlation analysis was used to determine the correlation between the AChR‐Ab concentration and clinical score. The changes in the antibody concentration and clinical score are shown in MGFA‐antibody concentration–treatment plots.ResultsAutoantibody detection tests were performed in 67 patients, and their clinical scores were recorded. Forty‐nine patients received immunosuppressive therapy, 17 patients received pyridostigmine only, and 1 patient under thymectomy without any medication. The AChR‐Ab concentration correlated with the MGFA Classification in 5 (29.4%) patients in the pyridostigmine‐only group and 15 (30.6%) patients in the immunosuppressive drug group. The changes in the MGFA Classification preceded the changes in the AChR‐Ab concentration in 4 (23.5%) patients treated with pyridostigmine and 10 (20.4%) patients on immunosuppressive drugs. In patients on oral non‐steroidal immunosuppressants, the AChR‐Ab concentration changed by more than 50%, whereas the MGFA Classification did not increase. The AChR‐Ab concentration decreased in 17/32 (53.1%) patients after thymectomy, and then increased, whereas the AChR‐Ab concentration increased in 15/32 (46.9%) patients and the MGFA Classification decreased in 27/32 (81.8%) patients after thymectomy. The AChR‐Ab concentration presented a slight correlation with the corresponding MGFA, QMG, and MG‐ADL in patients with thymoma.DiscussionIn the Chinese AChR‐MG population, the Changes in the AChR‐Ab concentration in individuals with AChR‐MG did not consistently correlate with the severity of clinical symptoms.

Impact of cancer type on the incidence of cutaneous toxicities after immune checkpoint inhibitor therapy: A population-level analysis.

e14553 Background: Cutaneous immune-related adverse events (cirAEs) from immune checkpoint inhibitor (ICI) therapy are increasing as these drugs are more widely used. Population-level studies are lacking. In this retrospective cohort study, we analyzed the primary tumor’s effect on cirAE incidence and downstream utilization of systemic immunosuppression in a national healthcare database (TriNetX). Methods: Index event was defined as day of ICI initiation; outcomes were restricted to 2 years from index. cirAEs were defined as 42 dermatoses identified in a comprehensive review of the cirAE literature (Sibaud 2018) and expert opinion. Systemic immunosuppression was classified as steroidal or non-steroidal. Primary outcomes included aggregate and cancer-specific incidence of cirAEs across the four most common cancer indications for ICI therapy (melanoma, lung, urinary, and gastrointestinal). Secondary outcomes included utilization of new steroidal or non-steroidal systemic immunosuppression. For each analysis, we excluded patients with an outcome prior to the index event. Risk ratios (RR) were calculated after 1-to-1 propensity score matching, adjusting for age at index, sex, race, ethnicity, and ICI target, with the lung cancer group as reference. Results: We identified 27,481 eligible subjects. Aggregate incidence of cirAEs across all cancer types was 23.41%, with non-specific rashes, pruritus, and drug eruptions as the most common diagnoses. Among all patients, new steroidal and non-steroidal immunosuppression use following ICI initiation was 16.1% and 4.1%, respectively. After adjusting for covariates, melanoma (RR 1.60, 95% CI 1.43-1.79, p &lt; 0.001) was associated with a higher risk of cirAE, while urinary and gastrointestinal tract cancers were not significantly different from the reference. Melanoma (RR 0.64, 95% CI 0.55-0.74), urinary tract (RR 0.71, 95% CI 0.62-0.81) and gastrointestinal tract (RR 0.46, 95% CI 0.39-0.53) cancers were all less likely to require steroidal immunosuppression (all p &lt; 0.001). However, patients with urinary tract cancer (RR 4.03, 95% CI 3.04-5.35) and melanoma (RR 2.44, 95% CI 1.75-3.40) were more likely to receive non-steroidal systemic immunosuppression (both p &lt; 0.001). Conclusions: Our results reinforce that ICI recipients commonly develop skin toxicities and provide robust evidence that melanoma is independently associated with their incidence. Furthermore, we found that patients with lung cancers received steroidal systemic immunosuppression most frequently, an intervention associated with poorer overall survival (Riudavets 2020). In contrast, patients with melanoma were more likely to receive non-steroidal immunosuppression. This study is the first population-based analysis of an irAE across tumor types and is proof-of-concept for future investigations into clinical risk factors in a large dataset.

Impact of multidisciplinary severe immunotherapy complication service on outcomes for cancer patients receiving immune checkpoint inhibition.

2654 Background: The exponential increase in FDA-approved indications for immune checkpoint inhibitors (ICI) in cancer care has resulted in therapeutic success but also in the occurrence of immune-related adverse effects (irAEs) that can represent a significant clinical challenge. On October 3 2017, the Massachusetts General Hospital (MGH) implemented the Severe Immunotherapy Complications (SIC) Service, a multi-disciplinary care team for patients hospitalized with irAEs. The objectives of this study were to evaluate the impact of SIC Service on 1) healthcare utilization and 2) patients outcomes. Methods: Using pharmacy and hospital admission databases, a list of patients was identified that both received ICI for a malignancy and were hospitalized with severe irAEs in the period prior to initiation of the SIC service and after SIC initiation. The pre-SIC period was defined as an admission between 4/2/2016 through 10/3/2017, and the post-SIC period as an admission from 10/3/2017 through 10/24/2018. The rate of readmission after the index hospitalization was the primary outcome. Secondary outcomes included lengths of stay (LOS) for both initial irAE admissions and readmissions, use of corticosteroids and non-steroidal second-line immunosuppression, ICI discontinuation, and inpatient mortality in the pre- and post-SIC periods. Results: Among 1169 patients treated in the pre-SIC service intervention period; 127 were hospitalized for irAE. Among 1159 patients treated in the post-SIC intervention 122 were hospitalized for irAE. SIC Service implementation was associated with a significant reduction in irAE readmission rates (post-SIC 14.8% vs. pre-SIC 25.9%; odds ratio [OR], 0.46; 95% CI, 0.22-0.95; p=0.036). The length of stay, rates of corticosteroid use, second-line immunosuppression, and ICI discontinuation for irAE, as well as inpatient mortality rates were not significantly different before and after SIC Service implementation. Conclusions: This is the first study to report that establishing a highly subspecialized care team focused on irAEs can be associated with improved clinical outcomes for patients receiving ICI therapy. Such care teams may play an essential part in optimizing irAE care.