Search Results (108)

Background and Objectives: Alcoholic hepatitis (AH) is a growing public health concern with its rising incidence and its contribution to nearly half of all cirrhosis-related deaths in the United States. In this systematic review, we aimed to comprehensively evaluate the current evidence and trials on the use of anti-interleukin-1 (anti-IL-1) drugs in patients with AH, assessing their efficacy and adverse events compared to routinely prescribed drugs like corticosteroids. Materials and Methods: A comprehensive literature search was conducted across five databases to identify randomized controlled trials (RCTs) evaluating the role of anti-IL-1 agents like canakinumab and anakinra among patients diagnosed with AH. Data was extracted and pooled in the form of mean and standard deviation for continuous variables and event and total for dichotomous variables. Results: Three RCTs were included for quantitative synthesis, encompassing 307 patients. Using canakinumab, 58% of patients showed improvement in histology. Prednisolone was associated with higher 90-day survival (90% vs. 70%; hazard ratio for death = 0.34, 95% CI 0.14–0.83, p = 0.018) and transplant-free survival. Overall, a higher incidence of acute kidney injury and new-onset cardiac disorders was noted in the anti-IL-1 arm when compared to placebo. Conclusions: This study concludes the lack of efficacy of anti-IL-1 agents in causing improvement in patient outcomes when compared to standard therapies. A higher incidence of adverse events was also noted in the anti-IL-1 arm. These results emphasize the need for future clinical trials to evaluate the use of anti-IL-1 agents in AH objectively. Full article

Background: The management of rheumatoid arthritis (RA) has advanced significantly with the introduction of biologic disease-modifying antirheumatic drugs (bDMARDs). Despite these therapeutic strides, RA prognosis remains profoundly affected by comorbid conditions, particularly cardiovascular and metabolic complications, which increase both morbidity and mortality. The role of bDMARDs in modulating comorbidities remains underexplored, with limited evidence on their effects across various non-RA conditions, such as respiratory, diabetic, and hematologic disorders. This systematic review aimed to evaluate the impact of bDMARDs on the progression and outcomes of comorbidities in RA patients, providing insights to guide personalized treatment approaches. Methods: This systematic review was registered in PROSPERO (CRD42022345903) and followed the PRISMA guidelines. Original research articles from PubMed and Scopus, published up to 18 July 2024, were included. Studies assessing the impact of bDMARDs on comorbidities in RA patients met the eligibility criteria. Results: A total of thirteen studies met the inclusion criteria. They were published from inception until July 2024. The studied comorbidities included pulmonary conditions (asthma, chronic obstructive pulmonary disease, and interstitial lung disease) (n = 2); diabetes (n = 3); anemia (n = 3); and malignancies (n = 3). The bDMARDs studied were tumor necrosis factor inhibitors (TNFis) (n = 9); Rituximab (n = 5); Tocilizumab (n = 5); Abatacept (n = 5); and Anakinra (n = 2). The most reported effects of bDMARDs on comorbidities were the following: (i) an exacerbation of pulmonary comorbidities for Abatacept and TNFis; (ii) patients switched to or initiated on Abatacept as their first targeted disease-modifying antirheumatic drug (tDMARD) showed directionally lower rates and costs of T2DM-related complications compared with patients switching to or initiating other tDMARDs; (iii) there was no difference between Abatacept and TNFis or Rituximab/Tocilizumab regarding diabetes treatment switching or intensification; (iv) Anakinra significantly reduced the HbA1c%; (v) decreased serum hepcidin levels and improvement in anemia were observed in patients treated with TNFis or Tocilizumab; and (vi) no decrease in overall survival time or the significant incident malignancy rate was noted in RA patients. Conclusions: Overall, bDMARDs appear safe for use in RA patients with comorbidities and may even provide specific benefits for conditions such as anemia and diabetes. These findings suggest that clinicians could consider tailoring biologic therapy based on each patient’s comorbidity profile, potentially enhancing both RA management and comorbidity outcomes. For instance, selecting biologics such as Anakinra or Tocilizumab might be advantageous for RA patients with concurrent diabetes or anemia, given their observed metabolic and hematologic benefits. This personalized approach could improve the quality of life and reduce healthcare costs by addressing RA and associated comorbidities more effectively. Full article

Chronic inflammation is an important contributor to the development of cardiovascular disorders, and inflammasomes, especially the NOD-like receptor protein 3 (NLRP3), are emerging as crucial mediators in this context. Inflammasomes are activated through receptor-mediated danger signals, such as cholesterol crystals and cellular damage products, thereby stimulating the secretion of pro-inflammatory cytokines, which sustains inflammation. This mechanism drives atherosclerosis (via plaque formation and destabilization), heart failure (via fibrotic remodeling), and pericarditis (via exacerbation of pericardial inflammation). Therapeutic approaches seek to block inflammasome activation or their pro-inflammatory pathways. Colchicine, interleukin-1 inhibitors (anakinra, canakinumab), and Sodium-Glucose Transport Protein 2 (SGLT2) inhibitors have a positive impact on cardiovascular inflammation. Various new compounds, such as MCC950, have been described as novel specific inhibitors of NLRP3. Further studies are needed to validate the effectiveness and safety of these treatments. Further elucidating the role of inflammasomes in cardiovascular disease could open the way to achieving more effective therapies, allowing for better management of high-risk cardiovascular patients. Full article

Familial Mediterranean Fever (FMF) is characterized by recurrent febrile attacks and serositis. While colchicine is the primary treatment for FMF, some patients present resistance or intolerance with respect to this drug. Anakinra—an IL-1 receptor antagonist—has demonstrated efficacy in colchicine-resistant or -intolerant FMF patients. Background and Objectives: This study aimed to evaluate the clinical characteristics, treatment duration, response to therapy, dose interval modifications, and long-term outcomes in FMF patients treated with anakinra. Materials and Methods: We retrospectively analyzed data from 68 FMF patients who were colchicine-resistant or -intolerant and received anakinra treatment. Results: The median patient age was 40.2 years, with a predominance of female patients (57.3%). The median follow-up duration for patients treated with anakinra was 34.2 months. Anakinra dosing was successfully extended in 30.8% of patients. Eight patients discontinued anakinra due to remission, with a median remission duration of 18.4 months. In a subgroup analysis of 57 patients treated with anakinra for at least 12 months, a significant decrease was observed in Pras scores at 0 months, 3 months, and 12 months, as well as in Erythrocyte Sedimentation Rate, C-reactive protein, and Serum Amyloid A values (all p < 0.001). Statistically significant decreases in 24 h proteinuria values were found between 0 and 3 months, 3 and 12 months, and 0 and 12 months (p = 0.011, p = 0.006, and p = 0.007, respectively). Anakinra use in pregnancy and kidney transplant recipients was well tolerated. Dose extension and treatment discontinuation in remission are feasible strategies. Conclusions: These findings support the use of anakinra as a good treatment option in selected patients. Full article

Rheumatoid arthritis and periodontitis are comorbidities that share mutual pathways. IL-1β is a pro-inflammatory cytokine that plays a crucial role in both diseases. One of the treatment options for rheumatoid arthritis is the use of an IL-1 receptor antagonist (IL-1RA) such as anakinra. Anakinra tempers the disease by decreasing bone resorption and it could possibly stimulate bone formation. Here, we investigate the effect of anakinra in a periodontal disease setting on osteoclastogenesis by co-culturing periodontal ligament fibroblasts (PDLFs) and peripheral blood mononuclear cells (PBMCs) that contain monocytes, a source of osteoclast precursors, as well as by culturing PBMCs alone. The effect of anakinra on PDLF-mediated osteogenesis was studied under mineralization conditions. To mimic a chronic infection such as that prevalent in periodontitis, 10 ng/mL of IL-1β was added either alone or with 10 µg/mL of anakinra. Osteoclastogenesis experiments were performed using co-cultures of PDLF and PBMCs and PBMCs only. Osteoclastogenesis was determined through the formation of multinucleated cells in co-cultures of PDLF and PBMCs, as well as PBMCs alone, at day 21, and gene expression through qPCR at day 14. Osteogenesis was determined by measuring alkaline phosphatase activity (ALP) per cell at day 14. Anakinra is effective in downregulating IL-1β mediated leukocyte clustering and osteoclastogenesis in the co-cultures of both PDLF and PMBCs and PBMCs alone. Gene expression analysis shows that IL-1β increases the expression of the osteoclastogenic marker RANKL and its own expression. This higher expression of IL-1β at the RNA level is reduced by anakinra. Moreover, IL-1β downregulates OPG expression, which is upregulated by anakinra. No effects of anakinra on osteogenesis were seen. Clinically, these findings suggest that anakinra could have a beneficial systemic effect on periodontal breakdown in rheumatoid arthritis patients taking anakinra. Full article

A growing number of systemic hereditary inflammatory diseases characterized by periodic fevers and elevated acute-phase proteins during flares has been linked to deregulated inflammasome function and excessive bioactivity of interleukin (IL)-1. All these conditions respond, at varying degrees, to the specific blockade of IL-1. The remarkable progress with IL-1 antagonists in treating hereditary inflammasome-based disorders has offered new hope for several patients with further non-hereditary autoinflammatory conditions from multifactorial backgrounds. The effectiveness of the IL-1 blockade has transformed our understanding and management of many complex diseases and highlighted the role of aberrant IL-1 signaling in enigmatic conditions, characterized by recurrent or continuous inflammation and a lack of a role for autoreactive T-cells or autoantibody production. To date, the long-term blockade of IL-1 has been found to restore the clinical equilibrium in systemic inflammasomopathies of childhood, and IL-1 inhibitors have become cardinal weapons in managing both monogenic innate immunity defects and a plethora of polygenic diseases occurring in children, including Still’s disease, Kawasaki disease, recurrent pericarditis, chronic non-bacterial osteomyelitis, and Behçet’s disease. Very few side effects have been reported with the long-term use of anakinra, rilonacept, or canakinumab, and their safety profile has been largely documented even in childhood. Further investigations into the role of inflammasomes in the pathogenesis of autoimmune conditions as well as brain degenerative or cardiovascular disorders can be expected, paving the way for precision medicine with benefits beyond inhibiting signaling by individual IL-1-family cytokines. Full article

Background: Subarachnoid hemorrhage (SAH) is a severe neurological condition with high mortality and morbidity rates, often exacerbated by secondary complications such as inflammation, cerebral vasospasm, and apoptosis. Proinflammatory cytokines, including interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6), play critical roles in these pathological processes. Anakinra, an IL-1 receptor antagonist, has demonstrated significant anti-inflammatory effects in various disease models. This study aimed to evaluate the efficacy of anakinra in mitigating inflammation, vasospasm, and apoptosis in an experimental rat model of SAH. Methods: Thirty-two male Sprague Dawley rats were divided into four groups: Control (healthy), SAH (no treatment), Saline (0.2 mL saline subcutaneously), and Anakinra (50 mg/kg subcutaneously, twice daily). Proinflammatory markers (CRP, TNF-α, IL-1, IL-6, and fibrinogen) were measured in serum and cerebrospinal fluid (CSF) at 3, 7, and 10 days post-SAH. Basilar artery diameter was evaluated histopathologically, and Caspase-3 expression was assessed immunohistochemically to determine apoptotic activity. Results: SAH significantly increased levels of CRP, TNF-α, IL-1, IL-6, and fibrinogen in both serum and CSF, reduced basilar artery diameter, and elevated Caspase-3 expression compared to the Control group. Saline treatment provided limited improvements, with inflammatory markers and histopathological parameters remaining elevated. Anakinra treatment significantly reduced inflammatory markers, restored basilar artery diameter, and lowered Caspase-3 expression, highlighting its efficacy in mitigating inflammation, vasospasm, and apoptosis. Conclusions: Anakinra effectively suppresses inflammation, alleviates cerebral vasospasm, and inhibits apoptosis in an experimental model of SAH. These findings suggest its potential as a therapeutic agent for managing SAH and its complications. Further research is needed to explore its clinical applicability and long-term effects. Full article

Schnitzler syndrome is a unique autoinflammatory disease, of which 747 cases have been described worldwide to date. The main features of the syndrome are a triad of recurrent urticaria, monoclonal IgM gammopathy, systemic inflammation associated with recurrent fever, joint and bone pain, and atypical bone remodeling (osteosclerosis). The abnormal activation of the NLRP3 inflammasome produces IL-1, which drives the disease pathology, but it also involves IL-6 and IL-18. Unlike other autoinflammatory diseases, Schnitzler syndrome lacks evidence of the gene divergence causing the abnormal activation of NLRP3. However, mutations in the MEFV and MYD88 genes can be associated with the development of the disease. Due to its rarity, diagnosing the disease can be a challenging task. IL-1 inhibitors (i.e., anakinra, canakinumab, and rilonacept) are prominent in the treatment of the disease, but the IL-6 receptor inhibitor tocilizumab and the Bruton’s tyrosine kinase inhibitor ibrutinib are also promising alternatives. In this summary article, we aim to provide a comprehensive overview of the clinical and molecular background of the disease and potential therapeutic targets, based on the cases reported so far. We diagnosed a patient who, to the best of our knowledge, represents the 748th documented case of this specific pathology. In the context of this patient, we would also like to draw attention to the potential pathogenic role of two novel gene mutations (variants of the MEFV gene “c.2084A>G” and the F2 gene “3′UTR c.*97G>A”). Full article

Sandhoff disease (SD) is a progressive neurodegenerative lysosomal storage disorder characterized by GM2 ganglioside accumulation as a result of mutations in the HEXB gene, which encodes the β-subunit of the enzyme β-hexosaminidase. Lysosomal storage of GM2 triggers inflammation in the CNS and periphery. The NLRP3 inflammasome is an important coordinator of pro-inflammatory responses, and we have investigated its regulation in murine SD. The NLRP3 inflammasome requires two signals, lipopolysaccharide (LPS) and ATP, to prime and activate the complex, respectively, leading to IL-1β secretion. Peritoneal, but not bone-marrow-derived, macrophages from symptomatic SD mice, but not those from pre-symptomatic animals, secrete the cytokine following priming with LPS with no requirement for activation with ATP, suggesting that such NLRP3 deregulation is related to the extent of glycosphingolipid storage. Dysregulated production of IL-1β was dependent upon caspase activity but not cathepsin B. We investigated the role of IL-1β in SD pathology using two approaches: the creation of hexb^−/−Il1r1^−/− double knockout mice or by treating hexb^−/− animals with anakinra, a recombinant form of the IL-1 receptor antagonist, IL-1Ra. Both resulted in modest but significant extensions in lifespan and improvement of neurological function. These data demonstrate that IL-1β actively participates in the disease process and provides proof-of-principle that blockade of the pro-inflammatory cytokine IL-1β may provide benefits to patients. Full article

Objective: Subarachnoid hemorrhage (SAH) is a life-threatening cerebrovascular condition that triggers a robust inflammatory response and cerebral vasospasm. This study aimed to evaluate the effects of anakinra, an interleukin-1 receptor antagonist, and tocilizumab, an interleukin-6 receptor antagonist, on inflammation and vasospasm in an experimental rat SAH model. Methods: Forty male Sprague Dawley rats (200–250 g) were randomly assigned to five groups: control, SAH, SAH + anakinra (ANA), SAH + tocilizumab (TCZ), and SAH + anakinra + tocilizumab (ANA+TCZ). SAH was induced by injecting non-heparinized arterial blood into the cisterna magna. Treatment groups received anakinra (50 mg/kg twice daily), tocilizumab (8 mg/kg once daily), or their combination for three days. Blood and cerebrospinal fluid (CSF) samples were analyzed for inflammatory markers (IL-1, IL-6, TNF-α, CRP), and histopathological evaluations were conducted to assess vasospasm and apoptosis. Results: SAH significantly increased pro-inflammatory cytokines (IL-1, IL-6, TNF-α, CRP) and fibrinogen levels in serum and CSF while reducing the basilar artery lumen diameter (p < 0.001). Anakinra and tocilizumab treatments significantly reduced inflammatory markers and vasospasm severity compared to the SAH group (p < 0.05). Combination therapy was more effective in reducing inflammation and vasospasm than either treatment alone (p < 0.05). Anakinra showed a stronger effect on IL-1 reduction, while tocilizumab was more effective in lowering IL-6 levels. The ANA+TCZ group exhibited a significant decrease in caspase activity, indicating reduced apoptosis (p < 0.05). Conclusions: Anakinra and tocilizumab effectively mitigated inflammation and vasospasm in an experimental SAH model, with combination therapy showing superior efficacy. These findings suggest that targeting both IL-1 and IL-6 pathways may be a promising therapeutic strategy for managing SAH complications. Further studies are warranted to evaluate long-term outcomes and clinical implications. Full article

Background: SARS-CoV-2 can trigger hyperinflammation, leading to severe COVID-19, presenting with pneumonia, acute respiratory distress syndrome (ARDS), and multiple organ failure. Specific biomarkers like leukocytes, CRP, NLR, AST, LDH, D-dimer, ferritin, and IL-6 are associated with disease severity. Anakinra, an IL-1 receptor antagonist, has been proposed to mitigate hyperinflammation, but its clinical efficacy remains uncertain. This study aimed to evaluate the effect of Anakinra on inflammatory biomarkers, oxygenation status, and survival outcomes in hospitalized patients with moderate to severe COVID-19 (according to the National Institute of Health severity scale), compared to standard treatment. Methods: A retrospective analysis included 65 patients (mean age 75.51 ± 9.54 years; 58.5% male, 41.5% female) hospitalized with moderate to severe COVID-19. Patients were divided into two groups: a control group receiving standard treatment (n = 24) and a target group treated with Anakinra (n = 41). Biomarkers and oxygenation status were assessed on Days 0, 3, and 7. Statistical analyses compared the groups for changes in leukocytes, NLR, CRP, AST, LDH, D-dimer, ferritin, and IL-6. Results: Anakinra treatment was associated with significant reductions in leukocytes, NLR, D-dimer, ferritin, IL-6, and CRP by Days 3 and 7. Improvements in oxygenation status were observed, although no survival benefits were noted. The control group showed no significant biomarker changes except for AST and LDH on Day 7. Conclusions: Anakinra demonstrated favorable effects on biomarkers and oxygenation in moderate to severe COVID-19 but did not improve survival. Further studies are needed to validate these findings. Full article

Vincristine, a vinca alkaloid, is used in chemotherapy protocols for cancers such as acute leukemia, Hodgkin’s disease, neuroblastoma, cervical carcinoma, lymphomas, breast cancer, and melanoma. Among the common adverse effects of vincristine is peripheral neuropathy, with most patients receiving a cumulative dose over 4 mg/m² who develop varying degrees of sensory neuropathy. The onset of vincristine-induced peripheral neuropathy can greatly affect patients’ quality of life, often requiring dose adjustments or the discontinuation of treatment. Moreover, managing vincristine-induced peripheral neuropathy is challenging, with few effective therapeutic strategies available. In the past decade, preclinical studies have explored diverse substances aimed at preventing or alleviating VIPN. Our review consolidates these findings, focusing on the analgesic efficacy and potential mechanisms of various agents, including pharmaceutical drugs, natural compounds, and antioxidants, that show promise in reducing neuropathic pain and protecting neural integrity in preclinical models. Key novel therapeutic options, such as metabolic agents (liraglutide), enzyme inhibitors (ulinastatin), antipsychotics (aripiprazole), interleukin-1 receptor antagonists (anakinra), hormones (oxytocin), and antioxidants (thioctic acid), are highlighted for their neuroprotective, anti-inflammatory, and antioxidant effects. Through this synthesis, we aim to enhance the current understanding of VIPN management by identifying pharmacological strategies that target critical molecular pathways, laying the groundwork for future clinical studies. By clarifying these novel pharmacological approaches and elucidating their mechanisms of action, this review provides a foundation for developing more effective VIPN treatment strategies to ultimately improve patient outcomes. Full article

Background: Allogeneic stem cell transplantation (allo-SCT) has seen limited use in treating multiple myeloma (MM), despite its potential to offer long-term survival or even cure through the graft-versus-myeloma effect. Its limited application is largely due to concerns over serious complications like infections and graft-versus-host disease (GVHD). The possibility of GVHD exacerbation when CAR-T cells are administered to patients previously treated with allo-SCT remains a topic of concern. Ciltacabtagene autoleucel (Cilta-cel) and idecabtagene vicleucel (Ide-cel) are CAR-T therapies that have been FDA-approved for relapsed/refractory (R/R) MM. A recent study using data from the CARTITUDE-1 trial has shown promising safety and efficacy of Cilta-Cel in patients with a prior history of allo-SCT. This report outlines our real-world experience with CAR-T treatment in such patients. The objective of this study is to assess the safety and effectiveness of CAR-T therapy in R/R MM patients who have previously undergone allo-SCT. Methods: We conducted a retrospective analysis of adult patients (18–70 years old) with R/R MM treated with CAR-T therapy as part of an institutional IRB-approved protocol. Data were collected on safety and efficacy outcomes from the institution’s records. Adverse events (AEs) were evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded based on American Society for Transplantation and Cellular Therapy (ASTCT) criteria. Efficacy metrics included overall response rate (ORR) and progression-free survival (PFS), analyzed through the Kaplan–Meier method, with PFS defined as the time from CAR-T initiation to disease progression or death. Results: Of the 56 patients treated with CAR-T therapy, 8 (14.3%) had previously undergone allo-SCT. These patients had a median of seven prior therapy lines (LOTs), compared to five LOTs in the non-allo-SCT group (p = 0.04). CAR-T infusion occurred a median of 98.8 months after allo-SCT, with a range from 57.9 months to 178.5 months. CRS occurred in 87.5% of the allo-SCT group versus 77.1% in the non-allo-SCT group (p = 0.48). One patient in the allo-SCT group developed hemophagocytic lymphohistiocytosis (HLH), requiring anakinra. At a median follow-up of 4.8 months, the ORR was 87.5% in the allo-SCT group versus 75% in the non-allo-SCT group (p = 0.4). Median PFS had not been reached for the allo-SCT group at the time of analysis compared to 11.9 months in the non-allo-SCT group (p = 0.5). No treatment-related mortality or acute GVHD was noted in the allo-SCT cohort. Conclusions: The study suggests that prior allo-SCT does not adversely affect the safety or efficacy of CAR-T therapy in patients with R/R MM. These findings highlight the need for further investigations with larger patient samples and longer follow-up to better understand the interaction between allo-SCT and CAR-T therapy. Full article

Background: the role of the R202Q (c.605G>A, p.Arg202Gln) missense variant of the MEFV gene has been debated as either a benign polymorphism or a potentially pathogenic mutation. We report and discuss here the case of a young female with corticosteroid-dependent recurrent pericarditis carrying the homozygous R202Q variant, exhibiting distinctive clinical features possibly influenced by this genetic variant. Methods: a 30-year-old woman with a previous diagnosis of cancer and recent respiratory infection presented with severe pleuritic chest pain, hypotension, tachycardia, and fever. Initial diagnostic evaluation indicated cardiac tamponade, and emergent pericardiocentesis was performed. Despite initial treatment with NSAIDs, colchicine, and corticosteroids, the patient experienced multiple recurrences. Genetic testing identified homozygous R202Q variant in the MEFV gene. Given the corticosteroid dependency and recurrent nature of her condition, IL-1 inhibitor anakinra was introduced, leading to significant improvement, although tapering below 150 mg per week failed to prevent recurrences. Results: the introduction of anakinra resulted in rapid symptom relief and resolution of pericardial effusion. However, attempts to taper or discontinue anakinra led to pericarditis recurrences. Ultimately, a maintenance dose of 50 mg every three days was established, which maintained remission for 18 months without recurrence. Despite multiple tapering attempts, further reduction in anakinra dosage was unsuccessful without triggering relapses. Conclusions: the R202Q variant, although typically considered benign, may contribute to an autoinflammatory phenotype resembling familial Mediterranean fever. This case underscores the potential pathogenicity of the homozygous R202Q variant in recurrent pericarditis and its responsiveness to IL-1 inhibition. In patients with corticosteroid-dependent recurrent pericarditis, genetic testing for the R202Q variant should be considered when anti-IL-1 drugs cannot be withdrawn. Further studies are warranted to elucidate the variant’s role in pericardial inflammation and guide personalized treatment strategies. Full article

Background: Although there is consensus to use immunoglobulins and corticosteroids as first-line treatments for multisystem inflammatory syndrome in children (MIS-C), the effectiveness of biological immunomodulators in patients refractory to standard therapy remains unclear. We aimed to outline real-world data on biological immunomodulators. Method: A literature search using Ovid-Medline, EMBASE, Cochrane CDSR, and KMBASE was conducted from September 2021 to August 2022; certainty of evidence was assessed via GRADE. Results: Among 258 studies, 10 were selected for analysis, of which 2 were observational studies (with control groups receiving standard therapy of either intravenous immunoglobulins and/or glucocorticoids) and 8 were single-arm studies. In all, 145 patients were treated with biological immunomodulators (anakinra (72; 49%) or infliximab (65; 44%)). In the first observational study, patients in the anakinra group initially exhibited a lower left ventricular ejection fraction than those in the control group. In the second study, patients in the infliximab group required less additional therapy and showed lower newly developed left ventricular dysfunction rate and reduced C-reactive protein levels. The clinical outcomes associated with each biological agent in single-arm studies were not reported individually. Conclusions: Biological immunomodulators are feasible therapeutic options for refractory MIS-C. Nevertheless, further research is warranted to demonstrate clinical efficacy. Full article