Use Of Immunomodulatory Agents Research Articles

Prothrombotic Profile in Patients with Active Multiple Myeloma and the Impact of Immunomodulators: The Roadmap-MM Study

Backround: Thromboembolism occurs in about 10% of patients with multiple myeloma (MM). The incidence of VTE is higher in newly diagnosed MM patients as compared to those with relapsed or refractory disease and it is higher during the first 3 to 6 months after the initial diagnosis and treatment initiation. Some of the treatments administered to patients with MM are independent risk factors for VTE. Immunomodulatory agents (IMiDs) among anti-myeloma treatments stand out as having a considerable prothrombotic effect. Recognizing the significant risk associated with the use of immunomodulatory agents (the International Myeloma Working Group (IMWG) 2014 statement, and the European Myeloma Network Guidelines in 2015 both included guidance on the prevention of VTE in MM patients who receive IMiDs. The prospective, longitudinal observational study ROADMAP-MM CAT was designed to explore alternative strategies for the development of risk stratification tools in patients with multiple myeloma. To this target we evaluated the baseline profile of hypercoagulability in multiple myeloma patients with various disease status. Blood borne hypercoagulabity partly consisted of enhanced thrombin generation, a common phenomenon in patients with malignancies . It remains to be seen whether this phenomenon appears for multiple myeloma patients during the physical course of the disease. Aim: We conducted a study to explore the relationship between stages of MM and alterations of various thrombosis-related biomarkers in patients with MM and their relationship with MM therapy. Materials and Methods Patients with MM (n=162) were recruited and stratified to the following groups: 59 newly diagnosed treatment-naïve patients (ND), 49 patients receiving IMiDs (IM), 52 in complete remission (CR) and 12 patients in partial remission on IMiDs (PR/IM). Patients on anticoagulant treatment were excluded from the study. The control group (CG) consisted of 30 healthy age and sex-matched individuals. Samples of platelet-poor plasma (PPP) were assessed for thrombin generation (TG) with the TF 5pM PPP-Reagent® on Calibrated Automated Thrombogram (Diagnostica Stago, France). Plasminogen activator inhibitor-1 (PAI-1), soluble endothelial protein C receptor (sEPCR), and soluble vascular cell adhesion molecule-1 (sVCAM-1), Procoag-PPL were measured using antibody-based ELISA kits (Invitrogen International Inc., CA, USA, and Diagnostica Stago, France ). TF expression MPC-derived microparticles (MPC-dMPs) were detected using a Zymuphen MP-TF activity kit (Hyphen BioMed, Neuville sur Oise, France). The upper and lower normal limits (LNL and UNL) were calculated by the mean±2 SD. Results A total of 162 patients were enrolled (age 66.0±12.0 yrs; 53% male). Distribution of disease stage was as follows: 32% ISS I, 23% ISS II, 45% ISS III. Bone disease was present in 71% of patients and 19% of patients had high risk cytogenetic lesions. Patients with ongoing MM (ND, IM, PR/IM) had significantly lower Peak, ETP and MRI as compared to the CG. In contrast, patients in CR had Peak, ETP, MRI values similar to the CG. Patients with PR had lower ETP and MRI values as compared to the CR group. In ND 9% had TG >UNL and 22% had TG<LNL. In IM 10% had TG>UNL and 67% had TG<LNL. None in PR/IM had TG>UNL and 35% had TG<LNL. In CR, 23% had TG>UNL and 12% had TG<LNL. MP-TF levels and PPL were higher in untreated MM (CR) patients compared to control. MP-TF and PPL levels decreased significantly after chemotherapy in PR/IM but MP-TF remained high at CR. The plasma concentrations, PAI-1, sEPCR, and sVCAM-1 were higher in MM patients than controls. , Treatment with IMDs reduced all biomarker levels gradually from PR/IM to CR (Table 1). Conclusion Patients with active MM showed attenuated TG which was enhanced in the presence of IMiDs treatment. Complete remission was associated with normalization of TG. The plasma concentrations, TF-MP , PAI-1, sEPCR, and sVCAM-1 were increased in MM patients suggesting vascular aggression which is followed by release of these markers that could contribute to the procoagulant environment. Attention should be paid to therapy-related thrombosis indeed the effect the suggested role of IMiDs in hypercoagulability does not seem to be confirmed and requires further studies .

Multi-Omics Endotypes in ICU Sepsis-Induced Immunosuppression.

It is evident that the admission of some patients with sepsis and septic shock to hospitals is occurring late in their illness, which has contributed to the increase in poor outcomes and high fatalities worldwide across age groups. The current diagnostic and monitoring procedure relies on an inaccurate and often delayed identification by the clinician, who then decides the treatment upon interaction with the patient. Initiation of sepsis is accompanied by immune system paralysis following "cytokine storm". The unique immunological response of each patient is important to define in terms of subtyping for therapy. The immune system becomes activated in sepsis to produce interleukins, and endothelial cells express higher levels of adhesion molecules. The proportions of circulating immune cells change, reducing regulatory cells and increasing memory cells and killer cells, having long-term effects on the phenotype of CD8 T cells, HLA-DR, and dysregulation of microRNA. The current narrative review seeks to highlight the potential application of multi-omics data integration and immunological profiling at the single-cell level to define endotypes in sepsis and septic shock. The review will consider the parallels and immunoregulatory axis between cancer and immunosuppression, sepsis-induced cardiomyopathy, and endothelial damage. Second, the added value of transcriptomic-driven endotypes will be assessed through inferring regulatory interactions in recent clinical trials and studies reporting gene modular features that inform continuous metrics measuring clinical response in ICU, which can support the use of immunomodulating agents.

Investigating the genetic contribution in febrile infection-related epilepsy syndrome and refractory status epilepticus.

Febrile infection-related epilepsy syndrome (FIRES) is a severe childhood epilepsy with refractory status epilepticus after a typically mild febrile infection. The etiology of FIRES is largely unknown, and outcomes in most individuals with FIRES are poor. Here, we reviewed the current state-of-the art genetic testing strategies in individuals with FIRES. We performed a systematic computational analysis to identify individuals with FIRES and characterize the clinical landscape using the Electronic Medical Records (EMR). Among 25 individuals with a confirmed FIRES diagnosis over the last decade, we performed a comprehensive review of genetic testing and other diagnostic testing. Management included use of steroids and intravenous immunoglobulin (IVIG) in most individuals, with an increased use of immunomodulatory agents, including IVIG, plasma exchange (PLEX) and immunosuppressants such as cytokine inhibitors, and the ketogenic diet after 2014. Genetic testing was performed on a clinical basis in almost all individuals and was non-diagnostic in all patients. We compared FIRES with both status epilepticus (SE) and refractory status epilepticus (RSE) as a broader comparison cohort and identified genetic causes in 36% of patients with RSE. The difference in genetic signatures between FIRES and RSE suggest distinct underlying etiologies. In summary, despite the absence of any identifiable etiologies in FIRES, we performed an unbiased analysis of the clinical landscape, identifying a heterogeneous range of treatment strategies and characterized real-world clinical practice. FIRES remains one of the most enigmatic conditions in child neurology without any known etiologies to date despite significant efforts in the field, suggesting a clear need for further studies and novel diagnostic and treatment approaches.

Invasive Pulmonary Aspergillosis: Not Only a Disease Affecting Immunosuppressed Patients.

Fungal infections have become a common threat in Intensive Care Units (ICU). The epidemiology of invasive fungal diseases (IFD) has been extensively studied in patients severely immunosuppressed over the last 20-30 years, however, the type of patients that have been admitted to hospitals in the last decade has made the healthcare system and ICU a different setting with more vulnerable hosts. Patients admitted to an ICU tend to have older age and higher severity of disease. Moreover, the number of patients being treated in ICU are often immunosuppressed as a result of the widespread use of immunomodulatory agents, such as corticosteroids, chemotherapy, and biological agents. The development of Invasive Pulmonary aspergillosis (IPA) reflects a different clinical trajectory to affected patients. The increasing use of corticosteroids would probably explain the higher incidence of IPA especially in critically ill patients. In refractory septic shock, severe community-acquired pneumonia (SCAP), and acute respiratory distress syndrome (ARDS), the use of corticosteroids has re-emerged in order to decrease unacceptably high mortality rates associated with these clinical conditions. It is also pertinent to note that different reports have used different diagnosis criteria, and this might explain the different incidence rates. Another layer of complexity to better understand current IPA data is related to more aggressive acquisition of samples through invasive respiratory examinations.

Factors for progressive pulmonary fibrosis in connective tissue disease-related interstitial lung disease.

Progressive fibrosis can occur in connective tissue disease (CTD)-related interstitial lung disease (ILD) and make the prognosis worse. This study aimed to investigate factors related to progressive pulmonary fibrosis (PPF) phenotype in CTD-ILDs. Medical records of patients diagnosed as CTD and ILD at a single, tertiary hospital in South Korea were retrospectively reviewed. Patients whose lung functions were followed up for more than a year were included in analysis. PPF was defined as forced vital capacity (FVC) declined ⩾10% or diffusion capacity of carbon monoxide (DLco) ⩾15%. Of 110 patients with CTD-ILD, 24.5% progressed into PPF. Rheumatoid arthritis (RA) and Sjogren's disease accounted for more than 63% of PPF. Compositions of CTD type were similar between PPF and non-PPF. Clinical characteristics and proportion of usual interstitial pneumonia (UIP) pattern on chest images were also similar between PPF and non-PPF. Approximately 10% of patients in both groups were treated with anti-fibrotic agents. Use of systemic steroids and/or other immunomodulating agents lowered the risk of developing PPF in CTD-ILD patients after adjusting for gender-age-physiology score and smoking status (adjusted odds ratio: 0.25, 95% confidence interval: 0.07-0.85). About a quarter of CTD-ILD progressed into PPF. The use of immunomodulating agents lowered the risk of developing PPF. To improve outcomes of patients, future studies need to detect patients at higher risk for PPF earlier and set up clinical guidelines for treatment strategies in the process of PPF.

Immunotherapy as a Promising Option for the Treatment of Advanced Chordoma: A Systemic Review

To summarize the function and efficacy of immunotherapy as an adjunctive therapy in the treatment of advanced chordoma. Literature search was conducted by two reviewers independently. Case reports, case series and clinical trials of immunotherapy for chordoma were retrieved systematically from Pubmed, Web of Science, Scoupus and Cochrane Library. Clinical outcome data extracted from the literature included median progression-free survival (PFS), median overall survival (OS), clinical responses and adverse events (AEs). All studies were published between 2015 and 2022. Twenty-two eligible studies were selected for systemic review. PD-1/PD-L1 immune checkpoint inhibitors (ICIs) were the most common used immunotherapy agents in chordoma, among which Pembrolizumab was the most frequently prescribed. CTLA-4 antibody was only used as combination therapy in chordoma. Dose Limiting Toxicity (DLT) was not observed in any vaccine targeting brachyury, and injection site response was the most frequent AV. The response evaluation criteria in solid tumors (RECIST) were the most generally used evaluation standard in chordoma immunotherapy, and none of the included studies employed the Choi criteria. No clinical data have demonstrated that CTLA-4 ICIs combined with PD-1/PD-L1 ICIs is more effective than ICIs monotherapy in treating chordoma, and ICIs in combination with other therapies exhibit more toxicity than monotherapy. PD-1/PD-L1 ICIs monotherapy is recommended as an immunotherapy in patients with advanced chordoma, which may even benefit PD-L1-negative patients. The brachyury vaccine has shown good safety in chordoma patients, and future clinical trials should focus on how to improve its therapeutic efficacy. The use of immunomodulatory agents is a promising therapeutic option, though additional clinical trials are required to evaluate their safety and effectiveness. RECIST does not seem to be an appropriate standard for assessing medications of intratumoral immunotherapy.

A Regional Observational Study on COVID-19-Associated Pulmonary Aspergillosis (CAPA) within Intensive Care Unit: Trying to Break the Mold.

The reported incidence of COVID-19-associated pulmonary aspergillosis (CAPA) ranges between 2.4% and 35% in intensive care unit (ICU) patients, and awareness in the medical community is rising. We performed a regional retrospective observational study including patients diagnosed with CAPA defined according to the Modified AspICU Dutch/Belgian Mycosis Study Group and CAPA-EECMM, from five different ICUs, admitted between March, 2020 and September, 2021. Forty-five patients were included. The median age was 64 (IQR 60-72), mostly (73%) males. At ICU admission, the median Charlson comorbidity index was 3 (2-5), and the simplified acute physiology score (SAPS)-II score was 42 (31-56). The main underlying diseases were hypertension (46%), diabetes (36%) and pulmonary diseases (15%). CAPA was diagnosed within a median of 17 days (IQR 10-21.75) after symptoms onset and 9 days (IQR 3-11) after ICU admission. The overall 28-day mortality rate was 58%, and at univariate analysis, it was significantly associated with older age (p = 0.009) and SAPS-II score at admission (p = 0.032). The use of immunomodulatory agents, p = 0.061; broad-spectrum antibiotics, p = 0.091; positive culture for Aspergillus on BAL, p = 0.065; and hypertension, p = 0.083, were near reaching statistical significance. None of them were confirmed in multivariate analysis. In critically ill COVID-19 patients, CAPA acquired clinical relevance in terms of incidence and reported mortality. However, the risk between underdiagnosis-in the absence of specific invasive investigations, and with a consequent possible increase in mortality-and over-diagnosis (case identification with galactomannan on broncho-alveolar fluid alone) might be considered. Realistic incidence rates, based on local, real-life epidemiological data, might be helpful in guiding clinicians.

Could treatment with immunomodulatory agents targeting IL-1, IL-6, or JAK signalling improve outcomes in patients with severe influenza pneumonia? A systematic and narrative review

Background: Influenza is a global cause of morbidity and mortality and a significant risk for a future pandemic infection. Host hyperinflammation, similar to that seen in COVID-19, may occur in response to influenza virus pneumonia, with Janus kinase (JAK) signalling and proinflammatory cytokines Interleukin (IL)-1 and IL-6 involved. Immune modulation treatment of hospitalised and critically ill COVID-19 patients, including with IL-6 and JAK inhibitors, has been found to be beneficial. Significant interest exists in the use of immunomodulatory agents targeting these pathways in the treatment of severe influenza pneumonia. Methods: We conducted a review with both systematic and narrative methods to assess whether, in patients with severe influenza pneumonia, treatment with immunomodulatory agents targeting IL-1, IL-6 or JAK signalling, in comparison to no immune modulation, is beneficial and improves clinical outcomes. Results: Our systematic search screened 5409 records and found no randomised controlled trials of IL-1, IL-6 or JAK immunomodulatory agents in patients with severe influenza pneumonia. To support this systematic search, we provide a narrative review of the biological rationale, previous use of these agents, including in hospitalised patients with COVID-19, and an overview of their safety profiles. Conclusions: Although immune modulation has proven successful in treating hospitalised and critically ill patients with COVID-19 and a biological rationale exists for testing these agents in influenza, no agents targeting IL-1, IL-6 or JAK signalling have been assessed in randomised controlled trials of patients with severe influenza pneumonia. This highlights a significant evidence gap.

Fungal complications with the new coronavirus infection COVID-19

BACKGROUND: The growth of fungal pathology observed in the last decade, including life-threatening invasive mycoses, is associated with the spread of immunodeficiency states of various etiologies. The COVID-19 pandemic has made a negative contribution, causing a significant increase in the number of patients with fungal complications.
 AIM: To characterize the types of fungal complications in the acute period of a new coronavirus infection COVID-19 based on an analysis of the clinical course and therapeutic tactics for managing the underlying disease.
 MATERIALS AND METHODS: The results of a bacteriological study of 1284 cultures from sputum samples of patients with suspected secondary pneumonia in COVID-19 are considered. The study included 404 cultures of various types of fungi. The analysis of the clinical picture was carried out in 70 patients with fungal complications of various localization, who were treated in a regional covid hospital. This group included the results of microbiological examination of sputum, bronchoalveolar lavage (BAL), scrapings from lesions in the oropharynx, urine, blood, biopsy and autopsy material. The study was conducted from April 01, 2020 to December 31, 2021. The patients were divided into subgroups depending on the isolated pathogen: Candida spp. ― 64 patients, and fungi (Aspergillus spp. and Mucor spp.) ― 6 patients; outcome of the disease: favorable 66, lethal 4.
 RESULTS: In the microbial landscape of the respiratory tract in patients with COVID-19, gram-negative microbial flora prevailed, one third of the cultures were represented by fungi. During the two years of the pandemic, the proportion of fungal cultures increased from 26.9% in 2020 to 34.2% in 2021, while maintaining sensitivity to amphotericin B and fluconazole in most cases. In 2021, there was a negative growth trend in the sputum of molds of the species Aspergillus spp. (5 cultures) and Mucor spp. (1 culture).
 Typical fungal complications of COVID-19 were: candidiasis stomatitis caused by Candida albicans (71%), candidiasis of other urogenital localizations in the form of candiduria (20%), lung damage of mixed viral-fungal etiology in isolated cases, leading to death due to invasive mycosis. Only fungal flora was isolated in 57.1% of cases, various combinations of fungal and bacterial flora in 42.9%. Candidiasis stomatitis was diagnosed on average on day 11.61.08 of COVID-19, which corresponded to days 2-3 of hospitalization. Preceding outpatient treatment, in most cases, included antibiotics and hormonal therapy with glucocorticosteroids. Urogenital Urogenital fungal infection was diagnosed on the 17.75.17 day of illness, on the second week of hospital treatment (8.03.11 days). Fungal flora in sputum was determined on average on the 18.54.33 day of illness, on the second third week of hospitalization against the background of intensive immunosuppressive therapy.
 CONCLUSION: Risk factors for the development of fungal complications are the age of patients older than 50 years, overweight and hypertension, uncontrolled use of antibiotics and glucocorticosteroids at the prehospital stage. Mycoses are recorded in both severe and moderate COVID-19. An additional factor in their development is immunosuppressive therapy of the underlying disease. The most formidable complication of the course of COVID-19, worsening the prognosis of survival, is the addition of fungi with invasive growth Aspergillus spp., Mucor, as well as the development of fungal-bacterial associations with damage to the lung tissue.
 In the context of the ongoing SARS-CoV-2 pandemic, the use of immunomodulatory agents, including the combined use of corticosteroids and targeted immunosuppressive drugs, it is important to develop a risk-based approach in diagnosis and treatment for patients at risk of generalized and invasive mycoses.

Expert consensus on the role of OM-85 in the management of recurrent respiratory infections: A Delphi study

ABSTRACT Recurrent infections of upper and lower respiratory tract have an important clinical and economic impact, which can be reduced through appropriate preventive measures, including the use of immunomodulating agents, such as OM-85, which proved to be effective and safe in both adults and children. Although OM-85 can be useful for the prevention of respiratory tract infections, it is still underused in clinical practice. In order to evaluate the level of awareness of the disease burden of recurrent respiratory infections in adults and children and to assess the level of agreement on the prophylactic and therapeutic approach to the disease, including the use of immunomodulants, a Delphi study was performed. A board of six experts in the field of respiratory infections was appointed to elaborate a series of statements covering four main topics (disease, prevention, OM-85, and future strategies), which were thereafter voted by a panel of 30 experts. Results showed that prevention is unanimously recognized as the most important intervention to reduce disease burden, and the use of immunomodulation to improve the effectiveness of vaccination is gaining increasing favor among clinicians. In this respect, OM-85 is recognized as the most studied immunomodulating agent currently available, whose efficacy and safety make it a valuable tool to optimize the management of recurrent respiratory infections in both adults and children. In particular, the combined use of OM-85 and influenza vaccine was recognized as an effective and safe approach to improve the current prevention strategies in order to reduce the burden of recurrent respiratory infections.

Ventilator-associated pneumonia in critically ill patients with COVID-19 infection: a narrative review.

COVID pneumonitis can cause patients to become critically ill. They may require intensive care and mechanical ventilation. Ventilator-associated pneumonia (VAP) is a concern. This review discusses VAP in this group. Several reasons have been proposed to explain the elevated rates of VAP in critically ill COVID patients compared to non-COVID patients. Extrinsic factors include understaffing, lack of personal protective equipment and use of immunomodulating agents. Intrinsic factors include severe parenchymal damage and immune dysregulation, along with pulmonary vascular endothelial inflammation and thrombosis. The rate of VAP has been reported at 45.4%, with an intensive care unit mortality rate of 42.7%. Multiple challenges to diagnosis exist. Other conditions such as acute respiratory distress syndrome, pulmonary oedema and atelectasis can present with similar features. Frequent growth of gram-negative bacteria has been shown in multiple studies, with particularly high rates of Pseudomonas aeruginosa. The rate of invasive pulmonary aspergillosis has been reported at 4–30%. We would recommend the use of invasive techniques when possible. This will enable de-escalation of antibiotics as soon as possible, decreasing overuse. It is also important to keep other possible causes of VAP in mind, e.g. COVID-19-associated pulmonary aspergillosis or cytomegalovirus. Diagnostic tests such as galactomannan and β-D-glucan should be considered. These patients may face a long treatment course, with risk of re-infection, along with prolonged weaning, which carries its own long-term consequences.

Management of noninfectious scleritis

Scleritis is a manifestation of inflammatory eye disease that involves the sclera. It can be divided into multiple subtypes, including diffuse anterior, nodular anterior, necrotizing, and posterior scleritis. In many cases, scleritis is restricted to the eye; however, it can occur in the context of systemic illness, particularly autoimmune and infectious conditions. Patients with autoimmune conditions, such as rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus, and polyangiitis with granulomatosis, may develop scleritis flares that may require topical and systemic therapy. Initial therapy typically involves oral nonsteroidal anti-inflammatory drugs (NSAIDs); however, it is important to address the underlying condition, particularly if systemic. Other treatment regimens typically involve either local or systemic steroids or the use of immunomodulatory agents, which have a wide range of efficacy and documented use in the literature. There is a myriad of immunomodulatory agents used in the treatment of scleritis including antimetabolites, calcineurin inhibitors, biologics, and alkylating agents. In this review, we highlight the various subtypes of noninfectious scleritis and explore each of the mainstay agents used in the management of this entity. We explore the use of steroids and NSAIDs in detail and discuss evidence for various immunomodulatory agents.

Immunomodulation for the Treatment of Chronic Chagas Disease Cardiomyopathy: A New Approach to an Old Enemy.

Chagas disease is a parasitic infection caused by the intracellular protozoan Trypanosoma cruzi. Chronic Chagas cardiomyopathy (CCC) is the most severe manifestation of the disease, developed by approximately 20-40% of patients and characterized by occurrence of arrhythmias, heart failure and death. Despite having more than 100 years of discovery, Chagas disease remains without an effective treatment, especially for patients with CCC. Since the pathogenesis of CCC depends on a parasite-driven systemic inflammatory profile that leads to cardiac tissue damage, the use of immunomodulators has become a rational alternative for the treatment of CCC. In this context, different classes of drugs, cell therapies with dendritic cells or stem cells and gene therapy have shown potential to modulate systemic inflammation and myocarditis in CCC models. Based on that, the present review provides an overview of current reports regarding the use of immunomodulatory agents in treatment of CCC, bringing the challenges and future directions in this field.

Sepsis-Induced Immunosuppression.

Sepsis is expected to have a substantial impact on public health and cost as its prevalence increases. Factors contributing to increased prevalence include a progressively aging population, advances in the use of immunomodulatory agents to treat a rising number of diseases, and immune-suppressing therapies in organ transplant recipients and cancer patients. It is now recognized that sepsis is associated with profound and sustained immunosuppression, which has been implicated as a predisposing factor in the increased susceptibility of patients to secondary infections and mortality. In this review, we discuss mechanisms of sepsis-induced immunosuppression and biomarkers that identify a state of impaired immunity. We also highlight immune-enhancing strategies that have been evaluated in patients with sepsis, as well as therapeutics under current investigation. Finally, we describe future challenges and the need for a new treatment paradigm, integrating predictive enrichment with patient factors that may guide the future selection of tailored immunotherapy.

Primary Amoebic Meningoencephalitis by Naegleria fowleri: Pathogenesis and Treatments

Naegleria fowleri is a free-living amoeba (FLA) that is commonly known as the “brain-eating amoeba.” This parasite can invade the central nervous system (CNS), causing an acute and fulminating infection known as primary amoebic meningoencephalitis (PAM). Even though PAM is characterized by low morbidity, it has shown a mortality rate of 98%, usually causing death in less than two weeks after the initial exposure. This review summarizes the most recent information about N. fowleri, its pathogenic molecular mechanisms, and the neuropathological processes implicated. Additionally, this review includes the main therapeutic strategies described in case reports and preclinical studies, including the possible use of immunomodulatory agents to decrease neurological damage.

COVID-19 and the Use of Immunomodulatory Agents in Ophthalmology

Immunomodulatory agents are often used in the systemic treatment of non-infectious uveitis. These drugs consist of corticosteroids, conventional immunosuppressives, and biological agents. As it is known that they suppress the immune system, the most important concern associated with immunomodulatory therapy (IMT) is the increased risk of infection. The World Health Organization declared COVID-19 a pandemic on 11 March 2020. Although severe acute respiratory distress syndrome secondary to SARS-CoV-2 infection may develop in all people, patients who receive IMT may be at higher risk in terms of both the transmission of the infection and more severe disease course. Therefore, guidelines on the management of patients receiving IMT due to uveitis during the pandemic are needed. In this review, we examined the immunomodulatory drugs used in the treatment of uveitis in terms of infectious complications and the data of patients who received IMT during the COVID-19 pandemic and discussed recommendations for the use of these drugs. According to the latest information, patients who receive IMT may continue their treatment as long as there are no disruptions in regular complete blood count (especially white blood cell count >4,000/μL) and liver and kidney function tests. Patients diagnosed with COVID-19 should be managed with a multidisciplinary approach.

Development of a Predictive Model of Multiple Myeloma (MM) Patient (pt) Outcomes Based on Treatment Class Transitions Using the Connect® MMpatient Registry

Development of a Predictive Model of Multiple Myeloma (MM) Patient (pt) Outcomes Based on Treatment Class Transitions Using the Connect® MMpatient Registry

PND70 Procedure Coding Versus Pharmacy-Dispensing Claims for Assessing Steroid Use in Patients with Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) and Primary Immunodeficiency Diseases (PIDD)

Accounting for high-dose systemic corticosteroid (SCS) use is critical for unbiased real-world studies of patients with inflammatory or immunological disorders. SCS administration may be recorded as procedural codes for injections/infusions (Healthcare Common Procedural Coding System; HCPCS) or pharmacy-dispensed medications (National Drug Code; NDC). Understanding the patterns of SCS coding is important for the valid design of real-world studies. US patients initiating immunoglobulin (IG) treatment for CIDP or PIDD were identified in IBM MarketScan Research Databases from 2008–2018 and 2012–2018, respectively; high-dose SCS use was determined. Patients identified by each coding system were compared. Among 3975 patients with CIDP and initiating IG, 1382 (34.8%) had prior high-dose SCS use, identified by HCPCS in 925 (23.3%) patients and NDC in 646 (16.3%) patients (non-mutually exclusive). Compared with NDC-identified patients, HCPCS-identified patients were older, more likely to be male, from Southern US, receiving outpatient IG, and have had back pain, central nervous system disorders, diabetes, dyslipidemia, hypertension, and osteoarthritis. HCPCS-identified patients were less likely to have deep vein thrombosis (DVT), opioid use, or prior use of immunomodulating agents. Among 17,931 PIDD patients initiating IG, 11,576 (64.6%) had prior high-dose SCS use, identified by HCPCS in 8826 (49.2%) patients and NDC in 6342 (35.4%) patients (non-mutually exclusive). Compared with NDC-identified patients, HCPCS-identified patients were older, more likely to be female, from Southern US, receiving outpatient IG, using Medicare, and more often had low Risk Vital Sign scores (disease severity algorithm) and have had cancer, fibromyalgia, inflammatory bowel disease, and obesity. HCPCS-identified patients were less likely to have had pneumonia or DVT. HCPCS and NDC identification of high-dose SCS use may elucidate differences in patient populations, which should be considered in real-world studies.

POS1197 IN DEPTH IDENTIFICATION OF RISK FACTORS FOR SEVERE COVID-19, REQUIRING HOSPITALIZATION, IN PATIENTS WITH INFLAMMATORY RHEUMATIC DISEASES: RESULTS OF A DUTCH NESTED CASE CONTROL STUDY (PRELIMINARY RESULTS)

Background:Several risk factors for severe COVID-19 have been identified1. An important question is whether in addition to these generic risk factors, patients with a potentially altered immune response, either by disease (inflammatory rheumatic diseases (IRDs)) or use of immunomodulatory agents (IA), carry a higher or lower risk of severe COVID-19. In addition, several other potential risk factors for severe COVID-19 have been suggested, such as vitamin D status and specific medication (NSAIDs, ACE-inhibitors)2.Objectives:To identify risk factors for severe COVID-19, requiring hospitalization, in patients with IRDs.Methods:Multicenter, unmatched nested case control study in four rheumatology centers in the Netherlands. Cases are IRD patients requiring hospitalization for COVID-19 between March 1st 2020 and May 31st 2020. Control patients are IRD patients not hospitalized for COVID-19 within this period and were included in a 1:4 ratio. Patient-, disease- and treatment characteristics were extracted (still ongoing) from electronic patient files, and a questionnaire was used to collect additional data (e.g. on behavioral aspects). Potential risk factors for severe COVID-19 were analyzed using unconditional logistic regression, corrected for confounders.Results:77 cases and 198 controls were included. 26 case patients died as a result of COVID-19, 14 were admitted to the ICU. Crude ORs for female sex, age, BMI and presence of one or more comorbidities were 0.46 (95% CI 0.27-0.29), 1.1 (95%CI 1.0-1.1), 1.0 (95%CI 0.98-1.1) and 3.0 (95%CI 1.7-5.2) respectively. Table 1 displays corrected OR, highlighted when OR <0.5/>2.0. Corrected ORs were not significantly increased for any IRD, but a trend for gout was present. Use of hydroxychloroquine (HCQ) shows a protective effect, while use of other csDMARDs than methotrexate or HCQ leads to a higher risk of severe COVID-19. Trends were present for increased risk for rituximab (RTX), glucocorticoids and ACE inhibitors, and protective effect for IL-6R blockers.Conclusion:The outcomes of this study are in agreement with other research regarding risk of severe COVID-19 related to IRDs and use of IA1. The suggested increased risk of severe COVID-19 in RTX use is of concern and should be monitored closely. Strengths of this study include low bias due to behavioral effects as only cases early in the pandemic were included, completeness of the determinants of interest and ultimately, it provides answers to a relevant and urgent question.

Strategies to Overcome High-Risk Multiple Myeloma.

Multiple myeloma (MM) patients with high-risk cytogenetics continue to have inferior outcomes despite recent advances in the treatment of MM. As defined by the International Myeloma Working Group, the presence of t(4;14), t(14;16), del(17p), t(14;20) and amplification of 1q are considered to be high-risk chromosomal abnormalities associated with poor survival. Despite the use of immunomodulatory agents, proteasome inhibitors, autologous stem cell transplantation, and anti-CD38 monoclonal antibodies, clinical trials of current therapies have not shown strong statistical evidence of being able to overcome the poor prognosis of high-risk disease. Novel treatment approaches are urgently needed to improve survival in this subset of MM patients.