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Purpose: To evaluate the effect of interleukin-6 (IL-6) inhibitor (tocilizumab) on bacterial infection-associated bone resorption around implants during osseointegration in rabbits. Materials and Methods: At total of 24 male, 9-monthold New Zealand white rabbits were included, and their two mandibular anterior teeth were extracted. Three months after extraction, 24 one-piece Dentium implants (Ø 2.5 mm, intraosseous length of 12 mm) were inserted in the anterior mandible, and the rabbits were divided into four groups (n = 6 per group). Different treatment methods were used in each group: blank control group (BC); only silk ligation (negative control [NC]); silk ligation and injection with minocycline hydrochloride ointment (positive control [PC]); and silk ligation and injection with tocilizumab at 8 mg/kg via the auricle vein (experimental [EP]). Eight weeks later, the animals were sacrificed, and samples were collected and then analyzed using microcomputed tomography (microCT) scanning, immunohistochemical analysis, and histologic analysis. Results: From the microCT measurement, the ratio of the bone volume to the total volume (BV/TV) in the EP group was 67.00% ± 2.72%, which was higher than that in the other three groups (58.85% ± 2.43% in the BC group, 55.72% ± 2.48% in the PC group, and 36.52% ± 3.02% in the NC group). From immunohistochemical analysis, the expression of IL-6 was found to be higher in the NC group than in the BC, PC, and EP groups, but there was no statistical difference between these three groups. Furthermore, the RANKL (receptor activator of nuclear factor-κB ligand) expression was the lowest in the EP group, followed by the BC group, the PC group, and the NC group, which had the highest expression; there was no difference between the NC and PC groups. Upon histologic analysis, significant new bone was found on the implant surfaces in the EP group, sparse and less new bone could be seen in the BC and PC groups, and the most serious bone resorption occurred in the NC group. Conclusions: Tocilizumab, an inhibitor of IL-6, has a certain effect in preventing bone loss around implants caused by bacterial infection during the osseointegration period. [ABSTRACT FROM AUTHOR]

Despite unprecedented survival in patients with glioblastoma (GB), the aggressive primary brain cancer remains largely incurable and its mechanisms of treatment resistance have gained particular attention. The cytokine interleukin 6 (IL-6) and its receptor weave through the hallmarks of malignant gliomas and may represent a key vulnerability to GB. Known for activating the STAT3 pathway in autocrine fashion, IL-6 is amplified in GB and has been recognized as a negative biomarker for GB prognosis, rendering it a putative target of novel GB therapies. While it has been recognized as a biologically active component of GB for three decades only with concurrent advances in understanding of complementary immunotherapy has the concept of targeting IL-6 for a human clinical trial gained scientific footing. [ABSTRACT FROM AUTHOR]

Objectives The aim of this study is to investigate the effect of anti-interleukin (IL)-1/-6 biologics on systemic juvenile idiopathic arthritis (sJIA)-associated macrophage activation syndrome (MAS). Methods Demographic, clinical and laboratory data of patients followed up with a diagnosis of sJIA-associated MAS assessed from sixteen paediatric rheumatology centres across the country. The clinical and laboratory features of MAS developing while on biological drugs were compared with those without this treatment. Results One hundred and sixty-two patients were included in the study. Forty-five of the MAS events were detected under the effect of anti-IL-1/-6 biologics, while the patients experiencing the remaining 155 events have not received biological treatment in the last three months. Platelet count [128 (72–232) vs 199 (130–371) 109/l], ferritin level on admission [1107 (676–2050) vs 2863 (1193–9562) ng/ml], C-reactive protein level [15.4 (2.9–56) vs 90 (32–160) mg/l], erythrocyte sedimentation rate [13 (3–36) vs 43.5 (13–77) mm/h] and fever duration [5 (4–7.5) vs 10 (7–14.3) days] were found lower in the group under the impact of anti-IL-1/-6 biologics. Among patients treated with biologics, 26.6% did not meet the published 2016 MAS classification criteria at presentation. The rates of hepatomegaly and splenomegaly were relatively lower in the canakinumab-treated group when compared with those receiving other biologicals or to patients, not on biologicals. Conclusion Anti-IL-1/-6 therapies can mask the clinical and laboratory features of MAS, and proposed guidelines for MAS classification criteria may not be met. [ABSTRACT FROM AUTHOR]

Objective: In this retrospective and cross-sectional study, it was aimed to evaluate the efficacy of tocilizumab (TCZ) treatment in critical COVID-19 patients who were hospitalized in the intensive care unit (ICU) and developed cytokine storm. Materials and Methods: The study included 219 critically ill COVID-19 patients followed in the ICU and treated with TCZ. All patients received 2 doses of 400 mg/day TCZ treatment during their stay in the ICU. Clinical conditions, laboratory data, inotrope requirement and chest radiographs before and after TCZ treatment were compared. Mortality rates at the 7th day, 28th day and total mortality rates of the patients were recorded. Results: It was observed that there was a significant decrease in CRP values over time after TCZ treatment. There was a significant increase in leukocyte, lymphocyte, lactate, urea, creatinine, AST, D-dimer, LDH and PCT values. The 7-day mortality of the patients was 21%, the 28-day mortality was 64.8%, and the total mortality rate was 65.3%. Conclusion: It was determined that after TCZ treatment, only CRP levels, which are among the inflammatory parameters, decreased significantly in patients, and the mortality rates were still high with the increase in the values of kidney and liver function tests of the patients. [ABSTRACT FROM AUTHOR]

Objectives Anti-IL-6 receptor antibodies are clinically efficacious in the management of RA with an associated increase in Tregs; however, the role of functional Treg subsets has yet to be clarified. This study aimed to evaluate how functional Treg subsets are altered by IL-6 receptor blockade and to analyse the relationship between these Treg subsets and the clinical outcome of RA. Methods We collected frozen peripheral blood mononuclear cells (PBMCs) from 40 patients with RA who started tocilizumab (TCZ) with or without MTX and 11 healthy controls (HCs). We fractionated Tregs with flow cytometry based on markers of phenotype and function and measured the proportions of detailed Treg subsets sequentially from baseline to week 52. Results The proportions of resting Tregs (rTregs) and rTregs+activated Tregs (aTregs) were significantly lower in RA patients at baseline than in HCs. The proportions of all those CD127low Tregs, rTregs, aTregs and rTregs+aTregs were significantly increased with TCZ treatment. In patients treated with TCZ without MTX, rTreg were increased. Patients with an increase in the proportion of rTregs at week 12 had significantly less arthritis flares during the observation period. Conclusions Blocking the IL-6 receptor with TCZ increased the proportion of rTregs, a functional Treg subpopulation. Patients with an early increase in rTregs showed a favourable treatment course and this increase in rTregs may reflect molecular remission induced by IL-6 signal inhibition. [ABSTRACT FROM AUTHOR]

Objective To investigate the safety and efficacy of subcutaneous tocilizumab (SC-TCZ) treatment in a long-term extension (LTE) of clinical trials in polyarticular or systemic juvenile idiopathic arthritis (pJIA or sJIA). Methods Patients with pJIA or sJIA from two open-label, 52-week phase 1b core trials of SC-TCZ who had adequate response per investigator assessment entered the LTE and continued SC-TCZ treatment according to body weight–based dosing regimens until commercial availability or up to 5 years. Pharmacokinetics, pharmacodynamics, and efficacy were assessed for up to 3 years, and safety for up to 5 years in the LTE. Results Forty-four patients with pJIA and 38 patients with sJIA entered the LTE. Tocilizumab trough concentrations were maintained within the range expected to provide clinical benefit (mean values: pJIA, ∼10 μg/ml; sJIA, ∼75 μg/ml over 3 years). Pharmacodynamic parameters (interleukin-6, soluble interleukin-6 receptor, erythrocyte sedimentation rate, C-reactive protein) were maintained throughout the LTE at levels achieved in the core trials. Inactive disease per American College of Rheumatology provisional criteria was reported for 90% (17/19) and 53% (8/15) of patients with pJIA and 91% (10/11) and 92% (12/13) of patients with sJIA in the <30 and ≥30 kg body weight groups, respectively. Serious adverse events in the LTE were reported in six patients with pJIA (13.6%; five serious infections) and five patients with sJIA (13.2%; one serious infection). Conclusion Patients with pJIA or sJIA experienced long-term disease control with SC-TCZ treatment. Long-term safety was consistent with the known tocilizumab safety profile. Clinical trial registration clinicaltrials.gov, NCT02165345 [ABSTRACT FROM AUTHOR]

Dermatitis has been reported after initiation of IL-6 receptor (IL-6R) inhibitors (IL-6Ri), while genetic association studies of atopic dermatitis (AD) have implicated IL-6R pathway signaling. However, causality remains unclear. As the indications for IL-6Ri expand, so do the clinical importance of determining whether there is mechanistic evidence linking it to AD. Our aim was to examine the association between IL-6Ri and risk of AD. To genetically mimic IL-6Ri, we selected single-nucleotide polymorphisms within or near the IL6R gene associated with C-reactive protein at genome-wide significance among 343,524 individuals. Genetic data were obtained from 10,788 individuals with AD and 30,047 controls of European ancestry. We used inverse variance–weighted and pleiotropy-robust methods and examined genetic confounding using colocalization. Analyses were replicated by using 13,473 Finnish and 2,385 East Asian individuals with AD. The results from 3 independent analyses were pooled by meta-analysis. Genetically proxied IL-6Ri was associated with increased risk of AD (odds ratio [OR] = 1.78 per 4.4-mg/L reduction in C-reactive protein level [95% CI = 1.28-2.48] [ P = 6.5 × 10–4]). The results were replicated using Finnish outcome data (OR = 2.07 [95% CI = 1.58-2.72] [ P = 1.57 × 10–7]) and Eastern Asian data (OR = 1.68 [95% CI = 1.12-2.54] [ P =.013]). Meta-analysis of 3 independent populations (OR = 1.89 [95% CI = 1.57-2.28] [ P = 2.68 × 10–11]) showed no evidence of heterogeneity (P =.65). We found no statistical evidence for pleiotropy or genetic confounding. This genetic investigation provides consistent evidence (across independent multiancestry populations) that IL-6R signaling is causally implicated in AD susceptibility. Clinicians should remain vigilant for adverse effects resembling AD when using IL-6R inhibitors for immune-mediated inflammatory diseases. [ABSTRACT FROM AUTHOR]

Anti-mitochondrial antibody (AMA)-positive myopathy, a recently identified condition with significant cardiac involvement, poses a serious challenge in treatment consensus due to its extreme rarity. While several studies demonstrate the efficacy of high-dose prednisolone in managing this disease, the current literature lacks substantial evidence regarding the effectiveness of biologic therapy or low-dose prednisolone for remission induction. Here, we present a case of AMA-positive myocarditis that emerged during rheumatoid arthritis treatment with tocilizumab (TCZ) and low-dose prednisolone (PSL). Successfully, intensive immunosuppressive therapy with high-dose PSL proved effective in stabilizing this condition. Our case highlights the necessity of a robust immunosuppressive approach, favoring high-dose PSL over the combination of low-dose PSL and TCZ in this disease. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 outbreak was declared a worldwide emergency as a result of its rapid spread. The number of people infected with COVID-19 is increasing rapidly around the world, and pneumonia can develop in COVID-19 cases. The monoclonal antibody tocilizumab blocks the interleukin-6 receptor, which in turn reduces inflammation. Aim: of the work The study aims to determine how tocilizumab affects inflammatory markers, laboratory indices, and oxygen therapy. Subjects and methods This retrospective observational study aimed to assess the effect of tocilizumab on inflammatory markers, laboratory parameters, and short-term outcomes in COVID-19 cases. Data was collected from 55 patients with COVID-19 who tested positive for SARS-CoV-2 using PCR. These patients were admitted to Ain Shams University Specialized Hospital—Obour between June 1, 2021, and May 31, 2022. Results: After tocilizumab administration, C-reactive protein levels decreased significantly, but there was no statistically significant change in hemoglobin, serum ferritin, or D-dimer levels. Following tocilizumab administration, the leukocyte counts, and platelet count increased significantly. There was a significant correlation between the presence of comorbidities in the studied patients (e.g., heart failure, post-renal transplantation, and hepatitis C virus) and the risk of mortality. The study's final result showed a significant decrease in platelet count in dead patients compared to discharged patients after receiving tocilizumab. Regarding oxygen therapy following tocilizumab administration, the use of face masks and non-rebreather facemasks was high in dead patients, while nasal prong usage was high in discharged patients. After receiving tocilizumab, there was an increase in the mean liters of oxygen required in dead patients compared to discharged patients. Conclusion: After administration of tocilizumab in COVID-19 hospitalized patients who have progressing disease, there was highly and significantly decrease in CRP level with no statistically significant alteration in the levels of hemoglobin, serum ferritin, and D-dimer and an increase in TLC and platelets was observed. Following tocilizumab administration, there was a decrease in oxygen demands, an improvement in oxygen therapy and oxygen saturation. Tocilizumab is a recommended therapy option. [ABSTRACT FROM AUTHOR]

Circular (circ) RNAs are non-coding RNAs with important functions in the nervous system, cardiovascular system, and cancer. Their role in atherosclerosis and myocardial infarction (MI) remains poorly described. We aim to investigate the potential circRNAs in immune cells during atherogenesis and examine the most regulated during MI and the modulation by interleukin (IL)-6 receptor inhibition by tocilizumab. Wild-type (WT) and ApoE−/− mice were fed an atherogenic diet for 10 weeks, and the circRNA profile was analyzed by circRNA microarray. Whole blood from patients with ST-elevated MI (STEMI) and randomized to tocilizumab (n = 21) or placebo (n = 19) was collected at admission, 3–7 days, and at 6 months, in addition to samples from healthy controls (n = 13). Primers for human circRNA were designed, and circRNA levels were measured using RT-qPCR. mRNA regulation of predicted circRNA targets was investigated by RNA sequencing. The expression of 867 circRNAs differed between atherogenic and WT mice. In STEMI patients, circUBAC2 was significantly lower than in healthy controls. CircANKRD42 and circUBAC2 levels were inversely correlated with troponin T, and for circUBAC2, an inverse correlation was also seen with final infarct size at 6 months. The predicted mRNA targets for circUBAC2 and circANKRD42 were investigated and altered levels of transcripts involved in the regulation of inflammatory/immune cells, apoptosis, and mitochondrial function were found. Finally, tocilizumab induced an up-regulation of circANKRD42 and circUBAC2 3–7 days after percutaneous coronary intervention. CircRNA levels were dysregulated in STEMI, potentially influencing the immune system, apoptosis, and mitochondrial function. [ABSTRACT FROM AUTHOR]

Introduction: Drug persistence may be a surrogate marker that reflects both long-term efficacy and safety in clinical settings, and tuberculosis (TB) is considered as one of the most important opportunistic infections after the biological treatment in rheumatoid arthritis (RA). We aimed to compare drug persistence and incidence of TB between tumor necrosis factor alpha (TNFα) inhibitors and tocilizumab in patients with RA using data from the Korean Health Insurance Review and Assessment Service database. Methods: In this analysis, 5449 patients with RA who started TNFα inhibitors, such as adalimumab, etanercept, infliximab, and golimumab or tocilizumab, as the first-line biological therapy between January 2014 and December 2017 were analyzed and followed up until December 2019. Drug persistence was defined as the duration from initiation to first discontinuation, and TB was defined as the prescription of > 2 anti-TB medications after the initiation of biologics. Results: TNFα inhibitors and tocilizumab were prescribed in 4202 (adalimumab, 1413; etanercept, 1100; infliximab, 769; golimumab 920) and 1247 patients with RA, respectively. During the analysis period, 2090 (49.7%) and 477 (38.3%) patients with RA discontinued TNFα inhibitors and tocilizumab, respectively, and 42 patients with RA developed TB (TNFα inhibitors, 33; tocilizumab, 9). After adjustment for confounding factors, TNFα inhibitors were significantly associated with a higher risk of discontinuation compared with tocilizumab (hazard ratio (HR) 1.63, p < 0.001). In subgroup analysis, all types of TNFα inhibitors, except for infliximab, demonstrated a significantly lower persistence rate compared with tocilizumab. There was no significant difference in TB incidence between tocilizumab and TNFα inhibitors. In subgroup analysis, infliximab has a significantly higher risk of TB compared with tocilizumab (HR 2.84, p = 0.02). Conclusion: In this analysis, tocilizumab had longer persistence than TNFα inhibitors with a similar incidence of TB. Our analysis has limitations: (1) The HIRA database lacks clinical details like disease activity and joint damage extent, potentially influencing the analysis results. (2) Reasons for discontinuing biological agents were not available. (3) TB diagnoses may be inaccurate because of missing microbiological results. (4) We did not analyze the impact of treating latent TB infection on TB development post-biological treatment, despite mandatory screening in Korea. [ABSTRACT FROM AUTHOR]

Background: Tocilizumab is commonly used for the management of chimeric antigen receptor (CAR) T‐cell therapy–associated cytokine release syndrome (CRS). However, it remains unknown whether tocilizumab or its dosage affects the efficacy and safety of CAR T‐cell therapy. The objective of this multicenter retrospective study was to explore the impact of tocilizumab on CAR T‐cell therapy. Methods: In total, 93 patients with B‐cell acute lymphoblastic leukemia (B‐ALL) receiving humanized anti‐CD19 CAR T cells were recruited from May 2016 to November 2022. Forty‐five patients received tocilizumab (tocilizumab group), whereas 48 patients did not (nontocilizumab group). Thirteen patients received >1 dose of tocilizumab. The primary end point was the effect of tocilizumab on the efficacy and safety of CAR T cells. Additionally, proliferation, killing, and cytokine assays of CAR T cells were performed in vitro in the presence of tocilizumab. Results: The median age of the patients was 33 years, with 47 males and 46 females. Patients in the tocilizumab group showed similar complete response (CR) rate, overall survival (OS), and event‐free survival (EFS) compared with the nontocilizumab group. Compared with patients who received ≤1 dose of tocilizumab, receiving >1 dose of tocilizumab did not affect their CR rate, OS, or EFS. In the tocilizumab group, all patients experienced CRS and 26.7% experienced immune effector cell–associated neurotoxicity syndrome (ICANS). In the nontocilizumab group, 64.6% of patients experienced CRS and 8.3% experienced ICANS. Up to 75% of ICANS and 87.5% of grade ≥3 ICANS occurred in the tocilizumab group. In vitro, tocilizumab did not impair the proliferation and killing effects of CAR T cells. Conclusions: Tocilizumab does not affect the efficacy of CAR T cells but may increase the likelihood of ICANS. Tocilizumab does not affect the efficacy of anti‐CD19 chimeric antigen receptor (CAR) T cells and the survival outcome of patients with B‐cell acute lymphoblastic leukemia. Tocilizumab may increase the likelihood of immune effector cell–associated neurotoxicity syndrome after CAR T‐cell therapy. [ABSTRACT FROM AUTHOR]

· CRP is not a reliable biomarker in tocilizumab-treated Takayasu arteritis. · IL-6 change at 6 months predicts long-term response to tocilizumab treatment. · Low IL-6 ratio (6-month to baseline) implies increased chance of sustained response. To explore the value of serial monitoring of serum interleukin-6 (IL-6) levels for predicting treatment response and occurrence of adverse events during tocilizumab (TCZ) treatment in refractory Takayasu arteritis (TAK). TAK patients receiving TCZ treatment were prospectively recruited and followed up at 1 month, 3 months and then every 3–6 months. Serum IL-6 levels were measured at each visit. Overall response was the combination of complete and partial response, requiring resolution of signs and symptoms, hsCRP and ESR level decreased at least by half, no progression on imaging and dose of glucocorticoid <15 mg/d. Thirty-five patients with a median follow up duration of 17 [9–44] months were included. The change of IL-6 after TCZ treatment for 6 months compared to the baseline was significantly lower in patients achieved overall response at 6, 12, 18 and 24 months. The ratio of IL-6 at 6 months to baseline could predict overall response at 12 and 24 months after TCZ treatment. With a cutoff value of 1.6, the sensitivity and specificity were 83.3 % and 87.5 % for 12 months, while 100 % and 88.9 % for 24 months. Patients with the ratio less than 1.6 were also 9 times more likely to achieve sustained improvement without treatment intensification. No correlation between IL-6 dynamics and occurrence of adverse events was found. The change of IL-6 levels after TCZ treatment for 6 months compared to the baseline can predict the overall treatment response at 12 months, 24 months and sustained improvement. [ABSTRACT FROM AUTHOR]

Objectives The efficacy of anti-IL-6 receptors such as tocilizumab (TCZ) was demonstrated in patients with PMR in two recent randomized controlled trials. The objective of this multicentre retrospective study was to assess the efficacy of TCZ in PMR patients requiring glucocorticoid (GC)-sparing treatment, as well as different strategies for TCZ withdrawal. Methods We conducted a multicentre study in French tertiary healthcare departments for patients with PMR. PMR patients receiving off-label TCZ between 2015 and 2022 were included. The primary endpoint was the proportion of patients tapering to GCs ≤5 mg/day 6 months after the first TCZ infusion. The secondary endpoints were the proportion in whom GC was discontinued during follow-up, and the proportion of patients in whom TCZ was discontinued. Results Fifty-three PMR patients were included. Thirty-one patients suffered from active PMR despite conventional synthetic DMARDs. GCs were ≤5 mg/day in 77% of the patients (95% CI 36–89) at 6 months, and in 97% of the patients at 12 months. Six and 12 months after the first TCZ infusion, the proportions of GC-free patients were 22.5% (95% CI 12.7–37.8) and 58.3% (95% CI 43.2–74.1), respectively. Among TCZ withdrawal strategies, TCZ infusion spacing and TCZ dose reduction were more successful (success in 87% and 79% of attempts, respectively) than TCZ discontinuation (success in 52% of attempts; P  = 0.012 and P  = 0.039, respectively). Conclusion In GC-dependent PMR patients, treatment with TCZ led to a drastic decrease in GC dose and remission of PMR. TCZ dose reduction or TCZ infusion spacing are good options to consider in TCZ withdrawal. [ABSTRACT FROM AUTHOR]

To determine the outcomes of intravenous (IV) tocilizumab (TCZ) in patients with non-infectious uveitis who failed with conventional immunomodulatory and anti-TNFα therapies. Records of seven patients with non-infectious uveitis treated with monthly IV TCZ (4–10 mg/kg) or biweekly IV TCZ (8 mg/kg) were reviewed. Outcome measures were changes in visual acuity, anterior chamber cell and flare grade, vitreous haze, central subfield thickness (CST), and fluorescein angiography (FA) score. Ten eyes of seven patients received TCZ therapy. Median age of patients was 14 (range, 7–24) years. Median duration of TCZ therapy was 15 (range, 5–32) months. Mean CST reduced from 373 ± 101.0 μm to 298.2 ± 40.3 μm. Mean FA score reduced from 12.5 ± 4.3 to 3.6 ± 2.6. One patient developed elevated liver transaminases. IV TCZ is a potentially effective and safe therapeutic option for the management of refractory non-infectious uveitis. [ABSTRACT FROM AUTHOR]

Introduction: Chimeric antigen receptor (CAR) T-cells have revolutionized cancer treatment, showing significant success, including treatment of pediatric B-cell acute lymphoblastic leukemia (B-ALL). Despite their efficacy, cytokine release syndrome (CRS) emerges as a common early adverse effect that can be life threatening in severe cases, resulting from the immune system's targeted activation against tumors. Areas covered: This review concentrates on CRS in children and young adults undergoing CAR T-cell therapy for B-ALL. It explores CRS pathophysiology, clinical presentation, and incidence, emphasizing the importance of a consensus definition and grading to homogenize the treatment according to the severity of symptoms. We will discuss the standard of care treatment of CRS but also novel approaches. We will highlight the importance of managing CRS without compromising the efficacy of immune cell activation against tumors. Expert opinion: As CAR T-cell therapy in pediatric B-ALL become increasingly available and used, optimal management of CRS becomes increasingly important. Early recognition and timely management has improved. Further information will aid us to identify optimal timing of tocilizumab and corticosteroids. Continued bench research coupled with clinical studies and biomarker discovery will allow for valuable insights into CRS pathophysiology and patient and/or cell-targeted treatments. [ABSTRACT FROM AUTHOR]

Purpose of the Review: To briefly review the latest updates in management in giant cell arteritis, an autoimmune vasculitis affecting the medium to large vessels. Recent Findings: Here, we review the known and newer trends in management of giant cell arteritis. While high dose glucocorticoids remain the mainstay of therapy, immunosuppressive medications are increasingly utilized to reduce the burden and risk of long-term glucocorticoid use. Published guidelines by the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) suggest early use of steroid-sparing immunosuppressive medications in patients with recently diagnosed or relapsing giant cell arteritis. Immunosuppressive medications include oral small molecules such as methotrexate and leflunomide and biologics, including the recently Federal Drug Administration (FDA) approved tocilizumab. Summary: Glucocorticoids remain the cornerstone of management for newly diagnosed disease but with the increasing use of medications such as IL-6 inhibitors, patients are decreasing steroid use within weeks, thereby limiting risks associated with long-term steroid use. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion This study reviewed the current knowledge and guidelines on managing COVID‐19 in children and proposed a practical approach to drug treatment.We analysed international guidelines from four prominent scientific bodies on treating COVID‐19 in children. These were the UK National Institute for Health and Care Excellence, the American National Institutes of Health, the Infectious Diseases Society of America and the Australian National Clinical Evidence Taskforce COVID‐19.Most paediatric patients with COVID‐19 only require symptomatic treatment. There was limited evidence on treatment recommendations for children with severe COVID‐19 or at risk of disease progression. However, several drugs are available for children and we have summarised the guidelines, in order to provide a concise, practical format for clinicians. All the guidelines agree that nirmatrelvir plus ritonavir or remdesivir can be used as prophylaxis for severe COVID‐19 in high‐risk patients. Remdesivir can also be used for severe COVID‐19 cases. Glucocorticosteroids are recommended, particularly in patients requiring oxygen therapy. Tocilizumab or baricitinib should be reserved for patients with progressive disease and/or signs of systemic inflammation.The guidelines provide useful advice and a degree of consensus on specific drug treatment for children with severe COVID‐19 or at risk of progression. [ABSTRACT FROM AUTHOR]

Background and aim: Different side effects, including infections, are encountered in patients receiving anticytokines used for the treatment of severe coronavirus disease 2019 (COVID-19). The aim of this study was to evaluate the infections and the effects of these infections that develop in this patient group. Materials and Methods: This study included 208 patients who were followed-up with the diagnosis of severe COVID-19 in two different hospitals. Patient data were obtained retrospectively from the hospital information system. Results: Of the 208 patients included, 54 were in the anakinra group, and 154 were in the tocilizumab group. Of these patients, 73 (35.1%) developed infection, 160 (76.9%) were admitted to the intensive care unit (ICU), and the 30-day mortality rate was 46.6%. The ICU admission, 30-day mortality, and infection rates were higher in the anakinra group, but it was not statistically significant (p = 0.137, p = 0.127, and p = 0.132, respectively), while pneumonia and bloodstream infection (BSI) rates were higher (p = 0.043 and p = 0.010 respectively). The 30-day mortality rate was significantly higher in patients who developed infection, especially in the tocilizumab group (p < 0.001 and p = 0.001). The independent risk factors affecting the development of infection were evaluated via regression analysis, in which it was found that age, sex, and the type of immunosuppressive treatment had no significant effect, while ICU admission increased the risk of infection by 32.8 times (95% CI: 4.4-245.8) and each day of hospitalization slightly increased the risk of infection by 1.06 times (95% CI: 1.03-1.09). Conclusion: Infection rates were higher in the anakinra group, especially the pneumonia and BSI rates were higher than in the tocilizumab group. The 30-day mortality rates were higher in patients who had an infection, especially in the tocilizumab group. This is one of the rare studies that evaluated infections developing in patients treated with anakinra and tocilizumab together. [ABSTRACT FROM AUTHOR]

Objectives: In clinical trials, tocilizumab (TCZ) is efficacious in patients with giant cell arteritis (GCA). This study evaluated the real-world tolerability and effectiveness of TCZ in Japanese patients with GCA. Methods: In this multicentre, prospective, Phase 4, large-scale, observational study, patients with GCA (with no TCZ treatment 6 months before the study) were recruited from 71 centres across Japan. Patients received subcutaneous TCZ 162 mg weekly (observation period, 52 weeks). Results: Of the 117 patients [female, 70.1%; mean age, 74.2 years; mean disease duration, 1.4 years; treated for new-onset GCA, 71.8%; presence of large-vessel lesions (LVLs), 61.5%; previous immunosuppressant use, 28.2%; glucocorticoids at baseline, 95.7% (mean: 22.4 mg/day)], 38.5% reported adverse events. The most common adverse events of special interest were neutropaenia and leukopaenia (7.7%), followed by serious infection (6.0%). The relapse-free proportion was 85.0%; relapse after remission, 6.0%; and no remission, 9.0%. At the last observation, 94.2% of relapse-free patients received a concomitant glucocorticoid dose of <10 mg/day. Fatigue, headache, neck pain, and absence of LVLs were positively associated with the relapse. Conclusions: TCZ was effective and well tolerated in Japanese patients with GCA and may be an effective treatment option combined with glucocorticoids. [ABSTRACT FROM AUTHOR]

This article presents a case study of a 53-year-old man with adult-onset Still's disease who developed streptococcal toxic shock syndrome (STSS) due to Streptococcus dysgalactiae subsp. equisimilis (SDSE) while receiving treatment with tocilizumab (TCZ), an anti-IL-6 receptor antibody. The article discusses the potential modifying effect of TCZ on the immune response and the pathophysiology of SDSE infection, which may have led to retroperitoneal panniculitis and atypical STSS. The case highlights the importance of considering the risk of infectious complications in patients receiving TCZ therapy. [Extracted from the article]

Pulmonary drug delivery offers a minimally invasive and efficient method for treating lung conditions, leveraging the lungs' extensive surface area and blood flow for rapid drug absorption. Nebulized therapies aim to deliver drugs directly to the lung tissue. This study investigates the histological impact of nebulized tocilizumab—a monoclonal antibody targeting IL-6, traditionally administered intravenously for rheumatoid arthritis and severe COVID-19—on a murine model. Thirty BALB/c mice were nebulized with tocilizumab (10 mg, 5 mg, and 2.5 mg) and six controls were nebulized with saline solution. They were euthanized 48 h later, and their organs (lungs, nasal mucosa, and liver) were analyzed by a microscopic histological evaluation. The results indicate that all the mice survived the 48 h post-nebulization period without systemic compromise. The macroscopic examination showed no abnormalities, and the histopathological analysis revealed greater lung vascular changes in the control group than in the nebulized animals, which is attributable to the euthanasia with carbon dioxide. Additionally, increased alveolar macrophages were observed in the nebulized groups compared to controls. No significant histological changes were observed in the liver, indicating the safety of nebulized tocilizumab. In conclusion, these findings suggest the potential of nebulized tocilizumab for treating pulmonary inflammation, warranting further research to establish its efficacy and safety in clinical settings. [ABSTRACT FROM AUTHOR]

Tocilizumab (TCZ) is increasingly used as a steroid‐sparing agent in giant cell arteritis (GCA), but there are strict Pharmaceutical Benefits Scheme (PBS) restrictions for its use in Australia. Patients who do not meet the PBS criteria can obtain TCZ through public hospital individual patient use (IPU) schemes which may not be universally accessible. We compared patients receiving IPU‐approved TCZ with patients receiving PBS‐subsidised TCZ and found IPU approvals were granted mainly for visual loss, a serious complication of GCA, in patients who otherwise failed to meet PBS criteria. Further studies demonstrating that TCZ is comparatively more effective than prednisolone monotherapy, as well as cost‐effective, are needed to substantiate the rationale for expanding PBS approval criteria. [ABSTRACT FROM AUTHOR]

Background and Objective: Tocilizumab is an immunoglobulin G1 monoclonal antibody targeting the interleukin-6 receptor (IL-6R). BAT1806/BIIB800 (tocilizumab-bavi) has been developed as a biosimilar to the reference product tocilizumab (TCZ). The objective of this study was to demonstrate physicochemical and functional similarity between BAT1806/BIIB800 and TCZ in a comprehensive comparability exercise. Methods: A comprehensive panel of over 20 methods was used to generate datasets comparing critical and non-critical product quality attributes for 10 BAT1806/BIIB800 lots and 44 TCZ lots (16 sourced from China, 16 from the EU, and 12 from the US). Primary structure, higher-order structure, and physicochemical properties were assessed using liquid chromatography, mass spectrometry, various spectroscopy techniques/methods, capillary electrophoresis, and thermoanalytical techniques. Fragment antigen-binding (Fab)- and fragment crystallizable (Fc)-mediated biological properties were assessed using cell-based assays, immunoassays, flow cytometry, and kinetic binding assays. Results: BAT1806/BIIB800 and TCZ (irrespective of source) were shown to be similar in terms of structural and functional properties. No differences were observed in terms of the most critical quality attributes, that is, soluble-IL-6R binding and inhibition of IL-6-mediated cell proliferation. BAT1806/BIIB800 and TCZ demonstrated similarity in terms of Fab- and Fc-mediated binding and biological activity. Minor differences were observed in glycosylation (afucosylation and sialylation), glycation, aggregation, and charge variants, which were demonstrated to be not clinically relevant. Conclusion: BAT1806/BIIB800 and TCZ were highly similar for all critical quality attributes. Where differences were observed in less critical quality attributes, additional analytical assessments and clinical study results determined these to be not clinically meaningful. [ABSTRACT FROM AUTHOR]

This article discusses the relationship between the timing of tocilizumab (TCZ) introduction and its glucocorticoid-sparing effects on adult-onset Still's disease (AOSD). A retrospective observational study was conducted on AOSD patients who received TCZ and high-dose glucocorticoids for remission-induction therapy. The study found that early introduction of TCZ within 3 weeks of initiating glucocorticoid treatment effectively reduced the glucocorticoid dose requirement without increasing adverse events or the risk of macrophage activation syndrome. However, further research is needed to determine the efficacy of early TCZ introduction in AOSD treatment. [Extracted from the article]

Introduction This study aimed to analyze the clinical course of TAFRO syndrome in patients through extended follow-up, focusing on recurrent cases and long-term remission. Methods This was a retrospective case series study. We assessed the clinical course of patients diagnosed with TAFRO syndrome between January 2012 and September 2022 at Toranomon Hospital or Toranomon Hospital Kajigaya, excluding those patients who died during the initial hospitalization. Results Twelve patients were included. Baseline characteristics, laboratory findings, treatment modalities, and outcomes were assessed. During the median follow-up period of 1474 days, two patients experienced recurrence following a reduction in tocilizumab (TCZ) dose, whereas two achieved remission for >400 days without TCZ treatment. The remaining eight patients maintained remission under the continued TCZ therapy. Recurrence diagnosis was complicated by the non-simultaneous presentation of the five manifestations of TAFRO syndrome. The patients who experienced recurrence showed milder manifestations and faster recovery than the initial onset. Glomerular endotheliopathy was evident in kidney biopsies during recurrence, which was similar to the initial presentation. In a case where only inflammation preceded other manifestation, a kidney biopsy was pivotal in distinguishing TAFRO syndrome relapse from other inflammatory conditions such as infection. Pretreatment serum IL-6 levels were within the reference range only in patients who experienced long-term remission without TCZ treatment. Conclusions This is the first study to perform kidney biopsies on recurrent TAFRO cases, highlighting recurrence after TCZ dosage reduction, non-simultaneous manifestation of symptoms, the utility of kidney biopsies in recurrence diagnosis, and potential non-IL-6 pathogenesis factors. Pretreatment serum IL-6 levels may help identify patients suitable for maintenance therapy without TCZ. Further investigation is warranted to identify stratified treatment approaches based on individual etiologic factors. [ABSTRACT FROM AUTHOR]

COVID-19-associated intensive care unit (ICU) admissions were recognized as critical health issues that contributed to morbidity and mortality in SARS-CoV-2-infected patients. Severe symptoms in COVID-19 patients are often accompanied by cytokine release syndrome. Here, we analyzed publicly available data from the Yale IMPACT cohort to address immunological misfiring and sex differences in early COVID-19 patients. In 2020, SARS-CoV-2 was considered far more pathogenic and lethal than other circulating respiratory viruses, and the inclusion of SARS-CoV-2 negative patients in IMPACT cohorts confounds many findings. We ascertained the impact of several important biological variables such as days from symptom onset (DFSO); pre-existing risk factors, including obesity; and early COVID-19 treatments on significantly changed immunological measures in ICU-admitted COVID-19 patients that survived versus those that did not. Deceased patients had 19 unique measures that were not shared with ICU patients including increased granzyme-B-producing GzB+CD8+ T cells and interferon-γ. Male COVID-19 patients in ICU experienced many more changes in immunological and clinical measures than female ICU patients (25% vs. ~16%, respectively). A total of 13/124 measures including CCL5, CCL17, IL-18, IFNα2, Fractalkine, classical monocytes, T cells, and CD4Temra exhibited significant sex differences in female vs. male COVID-19 patients. A total of nine measures including IL-21, CCL5, and CD4Temra differed significantly between female and male healthy controls. Immunosuppressed patients experienced the most decreases in CD4Temra and CD8Tem cell numbers. None of the early COVID-19 treatments were effective in reducing levels of IL-6, a major component of the cytokine storm. Obesity (BMI >30) was the most impactful risk factor for COVID-19-related deaths and worst clinical outcomes. Our analysis highlights the contribution of biological sex, risk factors, and early treatments with respect to COVID-19-related ICU admission and progression to morbidity and mortality.

Objective: In this retrospective and cross-sectional study, it was aimed to evaluate the efficacy of tocilizumab (TCZ) treatment in critical COVID-19 patients who were hospitalized in the intensive care unit (ICU) and developed cytokine storm. Materials and Methods: The study included 219 critically ill COVID-19 patients followed in the ICU and treated with TCZ. All patients received 2 doses of 400 mg/day TCZ treatment during their stay in the ICU. Clinical conditions, laboratory data, inotrope requirement and chest radiographs before and after TCZ treatment were compared. Mortality rates at the 7th day, 28th day and total mortality rates of the patients were recorded. Results: It was observed that there was a significant decrease in CRP values over time after TCZ treatment. There was a significant increase in leukocyte, lymphocyte, lactate, urea, creatinine, AST, D-dimer, LDH and PCT values. The 7-day mortality of the patients was 21%, the 28-day mortality was 64.8%, and the total mortality rate was 65.3%. Conclusion: It was determined that after TCZ treatment, only CRP levels, which are among the inflammatory parameters, decreased significantly in patients, and the mortality rates were still high with the increase in the values of kidney and liver function tests of the patients.

Abstract Background Equivalent efficacy and comparable pharmacokinetic, immunogenicity, and safety profiles of the biosimilar BAT1806/BIIB800 and reference tocilizumab (TCZ) in participants with moderate-to-severe rheumatoid arthritis (RA) have been reported up to week 24 (treatment period [TP] 1) of the phase 3 study. Here we present results for TP2 (study weeks 24–48). Methods In this phase 3, multicenter, multiregional, double-blind, active-controlled, equivalence study, participants with active RA despite methotrexate were randomized (1:1:2) to intravenous administration of 8 mg/kg TCZ every 4 weeks to week 48 (TCZ group), or TCZ to week 24 followed by BAT1806/BIIB800 to week 48 (TCZ to BAT1806/BIIB800 group), or BAT1806/BIIB800 to week 48 (BAT1806/BIIB800 group). Efficacy in TP2 was evaluated using American College of Rheumatology (ACR) response criteria (ACR20/50/70) and change from baseline in Disease Activity Score on 28 joints (DAS28). Pharmacokinetics (trough levels), safety, and immunogenicity were also evaluated. Results Of 621 randomized participants, 577 (92.9%) completed TP1 and entered TP2 (TCZ: N = 145 [93.5%]; TCZ to BAT1806/BIIB800: N = 142 [92.2%]; BAT1806/BIIB800: N = 290 [92.9%]). Proportions of ACR20 responders were similar between treatment groups throughout TP2 (87.8%, 90.3%, and 90.4%, respectively, at week 48), as were proportions of ACR50 and ACR70 responders, and reduction in DAS28. Drug trough levels and antidrug antibody incidences were comparable between the treatment groups. Adverse events were balanced across the treatment groups and no fatal events were reported. Conclusion In TP2, efficacy, safety, immunogenicity, and pharmacokinetic profiles were comparable between the TCZ, TCZ to BAT1806/BIIB800, and BAT1806/BIIB800 groups. Trial registration NCT03830203 and EudraCT 2018-002202-31.

Abstract Background The COVID-19 outbreak was declared a worldwide emergency as a result of its rapid spread. The number of people infected with COVID-19 is increasing rapidly around the world, and pneumonia can develop in COVID-19 cases. The monoclonal antibody tocilizumab blocks the interleukin-6 receptor, which in turn reduces inflammation. Aim of the work The study aims to determine how tocilizumab affects inflammatory markers, laboratory indices, and oxygen therapy. Subjects and methods This retrospective observational study aimed to assess the effect of tocilizumab on inflammatory markers, laboratory parameters, and short-term outcomes in COVID-19 cases. Data was collected from 55 patients with COVID-19 who tested positive for SARS-CoV-2 using PCR. These patients were admitted to Ain Shams University Specialized Hospital—Obour between June 1, 2021, and May 31, 2022. Results After tocilizumab administration, C-reactive protein levels decreased significantly, but there was no statistically significant change in hemoglobin, serum ferritin, or D-dimer levels. Following tocilizumab administration, the leukocyte counts, and platelet count increased significantly. There was a significant correlation between the presence of comorbidities in the studied patients (e.g., heart failure, post-renal transplantation, and hepatitis C virus) and the risk of mortality. The study's final result showed a significant decrease in platelet count in dead patients compared to discharged patients after receiving tocilizumab. Regarding oxygen therapy following tocilizumab administration, the use of face masks and non-rebreather facemasks was high in dead patients, while nasal prong usage was high in discharged patients. After receiving tocilizumab, there was an increase in the mean liters of oxygen required in dead patients compared to discharged patients. Conclusion After administration of tocilizumab in COVID-19 hospitalized patients who have progressing disease, there was highly and significantly decrease in CRP level with no statistically significant alteration in the levels of hemoglobin, serum ferritin, and D-dimer and an increase in TLC and platelets was observed. Following tocilizumab administration, there was a decrease in oxygen demands, an improvement in oxygen therapy and oxygen saturation. Tocilizumab is a recommended therapy option.

Elevated liver enzymes are commonly observed among adult-onset Still’s disease (AOSD), but severe acute liver failure is extremely rare. Although severe acute liver failure associated with AOSD poses a life-threatening condition, the appropriate treatment is unclear. Some case reports have demonstrated the efficacy of high-dose prednisolone (PSL) and cyclosporin A (CyA), although the adverse effects of CyA led certain patients to cease its use. Therefore, an alternative treatment option is crucial, and thus far, there have been no reports of tocilizumab (TCZ) being used for this severe phenotype. Here, we report the first case of successful treatment using TCZ as maintenance therapy for severe ALF associated with AOSD. Following initial treatment with high-dose PSL and CyA, our case was switched to TCZ due to CyA-related side effects including alopecia and tremors. Our case highlights TCZ as a potential option for maintenance therapy of this severe condition.

Introduction: Hemophagocytic lymphohistiocytosis (HLH) secondary to immune checkpoint inhibitors (irHLH) is rare, and consequently optimal management strategies remain to be defined. There are sparse reports of the successful treatment of irHLH with steroids and tocilizumab. This case adds to the body of literature supporting this management strategy. Case Description: We present a case of a patient with thoracic malignancy who received dual checkpoint inhibitors and developed weakness, fever, confusion, and cytopenias. Further testing revealed an extremely elevated ferritin level. Cytokine levels as well as HLH-2004 criteria and HScore results were consistent with irHLH. Clinical parameters and symptoms promptly improved after the administration of corticosteroids and tocilizumab. Conclusion: This case highlights an important treatment strategy for an immune checkpoint inhibitor toxicity associated with a high mortality rate.

Background Autoimmune encephalitis (AIE) is a group of inflammatory diseases characterized by the presence of antibodies against neuronal and glial antigens, leading to subacute psychiatric symptoms, memory complaints, and movement disorders. The patients are predominantly young, and delays in treatment are associated with worse prognosis.

Abstract Background The aim of this prospective observational cohort study was to unveil the predictors of treatment response to tocilizumab (TCZ) therapy in rheumatoid arthritis (RA) patients, in terms of clinical characteristics and serum proinflammatory cytokines, especially to explore the predictive value of granulocyte macrophage-colony stimulating factor (GM-CSF). Methods Active adult RA patients with inadequate response to MTX intending to receive TCZ therapy were recruited prospectively in the study. A total of 174 severe RA patients were included for the identification of the associations between treatment response and the following characteristic features: demographics, medications, disease activity, serum proinflammatory cytokines and so on. Results Disease duration (OR = 0.996), tender joint count (TJC)/68 (OR = 0.943), neutrophil ratio (W4/baseline) (OR = 0.224), the high level of GM-CSF > 5 ng/ml (OR = 0.414) at baseline were the independent adverse predictors of good response assessed by clinical disease activity index (CDAI) at week 24 (W24) for TCZ therapy in RA patients. Moreover, DAS28-ESR (OR = 2.951, P = 0.002) and the high level of GM-CSF > 10 ng/ml at baseline (OR = 5.419, P = 0.002) were independent predictors of poor response, but not the high level of GM-CSF > 5 ng/ml (OR = 2.713, P = 0.054). The patients in the high GM-CSF group had significantly higher DAS28-ESR and serum levels of cytokines (IL-17A, IL-1β, IL-6, TNF-α) at baseline, as well as significantly higher rate of non-good response (62.8% vs. 39.4%, P = 0.010) and poor response (27.9% vs. 9.1%, P = 0.004) than the low GM-CSF group at W24. In addition, poor responders had significantly higher levels of GM-CSF with concomitant increase in the serum levels of IL-17A and IL-1β at baseline than those in moderate and good response groups, while serum levels of IL-6 and TNF-α at baseline were not significantly different in three response groups. Conclusion The high levels of GM-CSF (> 5 ng/ml and > 10 ng/ml) at baseline were the independent predictors of non-good response and poor response to TCZ at W24 respectively. The high level of GM-CSF at baseline is a marker of high disease activity and a predictor of poor response to TCZ in severe RA patients, which may facilitate the development of individualized treatment strategies for refractory RA.

Anti-mitochondrial antibody (AMA)-positive myopathy, a recently identified condition with significant cardiac involvement, poses a serious challenge in treatment consensus due to its extreme rarity. While several studies demonstrate the efficacy of high-dose prednisolone in managing this disease, the current literature lacks substantial evidence regarding the effectiveness of biologic therapy or low-dose prednisolone for remission induction. Here, we present a case of AMA-positive myocarditis that emerged during rheumatoid arthritis treatment with tocilizumab (TCZ) and low-dose prednisolone (PSL). Successfully, intensive immunosuppressive therapy with high-dose PSL proved effective in stabilizing this condition. Our case highlights the necessity of a robust immunosuppressive approach, favoring high-dose PSL over the combination of low-dose PSL and TCZ in this disease.

Introduction. The deregulated excessive pro-inflammatory cytokine secretion has a detrimental impact on the evolution of COVID-19, aggregating tissue impairment, organ failure, and increasing the risk for death. Several studies have demonstrated the beneficial effect of Tocilizumab (TCZ) in reducing hyperimmune response in severe forms of COVID-19. Materials and methods. This study is a retrospective cohort consisting of a sample of 66 patients hospitalized with COVID-19. The 1-st group consists of 33 patients treated with TCZ 200 mg IV once, and the 2-nd group – of 33 patients treated with TCZ 400 mg IV once. Results. The average age of the patients included in the study was 58,22±1,38 years. A decision regarding TCZ administration was made on average on the 11,34±0,31 day of the disease when the beginning of Cytokine Storm was suspected in the patients already on dexamethasone treatment. The dose of TCZ had significance on the duration of patients' disabilities, duration of oxygen therapy, and duration of hospitalization, with better results for TCZ 400 mg vs. TCZ 200 mg. However, we cannot prove that the dose of TCZ influences the percentage of patients transferred to the ICU for invasive or non-invasive ventilation. Conclusion. The 200 mg fixed dose of TCZ can be a life-saving option for severely ill patients with COVID-19 in the context of IL-6 inhibitor supply shortages.

OBJECTIVE: There are many kinds of biological agents for the treatment of rheumatoid arthritis in clinic, but the differences in therapeutic efficacy and safety are still unclear. The purpose of this study is to compare the differences in effectiveness and safety of different biological agents for the treatment of rheumatoid arthritis. METHODS: CNKI, VIP, WanFang, China Biomedical Literature System, PubMed, Cochrane Library, Web of Science, and Embase databases were searched to collect the randomized controlled trials on biological agents for rheumatoid arthritis that meet the requirements from inception to October 1, 2022. The literature was selected by EndNote software, and the quality of the included literature was evaluated by RevMan 5.3 software. The software Stata 14.2 was used for direct meta-analysis and network meta-analysis of ACR20 (American College of Rheumatology 20% response), ACR50 (American College of Rheumatology 50% response), ACR70 (American College of Rheumatology 70% response), erythrocyte sedimentation rate, and adverse reactions. RESULTS: Totally 39 articles were included, including 5 low-risk articles, 4 high-risk articles, and the remaining 30 articles contained unknown risk bias, with a total of 13 treatment measures. The results of network meta-analysis: (1) In ACR20, infliximab combined with methotrexate (OR=5.54, 95%CI: 1.33-23.01, P < 0.05), abatacept+methotrexate tablets (OR=3.21, 95%CI: 1.13-9.10, P < 0.05), and tocilizumab (OR=2.95, 95%CI: 1.61-5.44, P < 0.05) were better than methotrexate tablets. The probabilistic ranking of ACR20 was: infliximab+methotrexate tablets > abatacept+methotrexate tablets > tocilizumab > certlizumab > etanercept+methotrexate tablets. (2) In the aspect of ACR50, etanercept combined with methotrexate tablets (OR=4.04, 95%CI: 2.13-7.66, P < 0.05), infliximab combined with methotrexate tablets (OR=4.79, 95%CI: 1.19-19.26, P < 0.05), and tocilizumab combined with methotrexate tablets (OR=3.54, 95%CI: 1.36-9.22, P < 0.05) had better therapeutic effects than methotrexate tablets. The probabilistic ranking of ACR50 was: etanercept+methotrexate tablets > infliximab+methotrexate tablets > tocilizumab+methotrexate tablets > tocilizumab > certlizumab+methotrexate tablets. (3) In terms of ACR70, the therapeutic effects of infliximab combined with methotrexate tablets (OR=8.00, 95%CI: 2.31-27.69, P < 0.05), etanercept combined with methotrexate tablets (OR=4.26, 95%CI: 2.51-7.21, P < 0.05), and tocilizumab combined with methotrexate tablets (OR=3.51, 95%CI:1.82-6.80, P < 0.05) were better than methotrexate tablets. The probabilistic ranking of ACR70 was infliximab+methotrexate tablets > etanercept+methotrexate tablets > tocilizumab+methotrexate tablets > certlizumab > adalimumab+methotrexate tablets. (4) In erythrocyte sedimentation rate, etanercept combined with methotrexate tablets (SMD=-9.23, 95%CI: -16.55 to -1.92, P < 0.05) was better than etanercept and methotrexate tablets (SMD=14.59, 95%CI: 7.28-21.91, P < 0.05). The probabilistic ranking of erythrocyte sedimentation rate was etanercept+methotrexate tablets > infliximab+methotrexate tablets > etanercept > adalimumab+methotrexate tablets > methotrexate tablets. (5) In terms of adverse reactions, placebo (OR=0.62, 95%CI: 0.39-0.99, P < 0.05) was better than infliximab and certlizumab (OR=0.44, 95%CI: 0.25-0.78, P < 0.05). The probabilistic ranking of adverse reactions was placebo > infliximab > etanercept+methotrexate tablets > certlizumab > etanercept. CONCLUSION: Based on evidence from 39 randomized controlled trials, infliximab combined with methotrexate tablets (highly recommended) can be the first choice in clinic, and etanercept combined with methotrexate tablets (highly recommended) can be the second choice in terms of good effectiveness and safety. [ABSTRACT FROM AUTHOR]

Randomized controlled trials have recently shown that both the IL-6 inhibitor Tocilizumab and the antifibrotic Nintedanib are efficacious for Systemic Sclerosis (SSc)-associated progressive interstitial lung disease (ILD). Since real-world clinical data on Tocilizumab/Nintedanib combination are lacking, we report on their long-term safety and efficacy. Consecutive patients who received off-label Tocilizumab for SSc plus Nintedanib for progressive ILD were retrospectively studied. Adverse events, and changes in Forced Vital Capacity (FVC), Diffucing Capacity for Carbon Monoxide (DLCO) and high resolution chest tomography (HRCT) between baseline and 6 and 12 months were assessed. Tocilizumab/Nintedanib combination was well tolerated by all 20 patients [aged 52 ± 13 years (mean ± SD), 14 women, 15 diffuse SSc, disease duration of 5.7 ± 4.9 years]; 7 of 20 patients received concomitant mycophenolate mofetil safely. No serious adverse events or laboratory abnormalities were noted. Five patients developed persistent diarrhea and 2 of them reduced dosage of Nintedanib. Baseline FVC (74%±12%) and DLCO (45%±10%) remained overall stable both at 6 months (73.5%±13% and 46%±11%, respectively) and 12 months (73%±14% and 45%±11%, respectively), regardless of disease duration. The extent of fibrotic reticular pattern in available pairs of HRCTs (n = 12) remained also stable at 12 months, whereas proportion (%) of ground glass opacities decreased from 29%±16 to 21%±14% (p = 0.048); improvement in HRCTs by almost 75% was noted in 2 of these12 patients. Tocilizumab/Nintedanib combination for one year was safe and stabilized lung function in real-world SSc patients with progressive ILD. Additional studies of this combination treatment in SSc-ILD are warranted. [ABSTRACT FROM AUTHOR]

Background: Cases of psoriasis associated with Tocilizumab (TCZ) are scarce. Objective: To describe a new case of TCZ-associated psoriasis and to perform a case-based review of similar cases. Methods: We searched Medline/Pubmed, Embase, Scopus, Web of Science, and Directory of Open Access Journals databases using the terms « Tocilizumab » and « Psoriasis » in the French and English literature. Results: We report a 70-year-old woman with a history of Rheumatoid Arthritis who developed Infliximab-induced plaque psoriatic eruption of the soles and palms, that resolved after Infliximab interruption, then relapsed after TCZ relay, and eventually resolved after TCZ interruption. Including our case, we identified 16 cases of TCZ-induced psoriatic eruption. Three (21%) out of 14 patients had a history of cutaneous psoriasis – data were not available for 2 patients. Eight (50%) patients had previously received TNFα antagonists. TCZ was stopped for 10 patients and continued for 4 patients. For the 2 remaining patients, the interval between two injections of TCZ was shortened. All the patients with available follow-up data had an improvement of the eruption within 4 weeks. Conclusion: To conclude, in case of TCZ-induced psoriatic eruption and in light of the published cases, we suggest using topical steroids and reassessing the patient 4 weeks later. If no healing is obtained, we suggest stopping TCZ, and treating the underlying disease with another drug. When no other drug is available, while waiting for more data regarding the value of IL-6 levels, it can be discussed to increase TCZ regimen, as it has been successful for 2 authors. Efficacy assessment of the chosen attitude should not take place before 4 weeks. [ABSTRACT FROM AUTHOR]

Giant Cell Arteritis (GCA), also known as Temporal Arteritis, is a type of large vessel vasculitis primarily affecting the elderly population. It typically manifests with headaches, visual impairment, and jaw claudication. Although third nerve palsy as the primary presentation of GCA is rare, it has been reported in previous instances. In this report, we describe the case of a patient presenting with pupil-sparing third nerve palsy, ultimately diagnosed with GCA, and successfully managed with steroids and tocilizumab. A lady in her 80s with past medical history of well-controlled hypertension, bladder cancer in remission, a twenty-pack year smoking history, cervical and lumbar spine stenosis, and recent immunizations presented with acute onset of right-sided pupil-sparing third nerve palsy. Labs were pertinent for an elevated ESR and CRP. Brain imaging was without acute abnormalities. A temporal artery biopsy established evidence of healed arteritis and a diagnosis of GCA was made. The patient was treated with pulse-dose steroids followed by an oral steroid taper and tocilizumab. At one month follow-up, there was partial resolution in her ophthalmoplegia. We underscore the importance of considering temporal arteritis as a potential cause of third nerve palsy in the elderly before attributing it solely to microvascular ischemia, particularly in patients with constitutional features. Additionally, in our comprehensive literature review, we aim to consolidate the existing data from similar presentations, shedding light on the clinical manifestation and disease trajectory. [ABSTRACT FROM AUTHOR]

Objective: To systematically evaluate the efficacy of subcutaneous tocilizumab in the treatment of patients with severe COVID-19 and provide evidence for the rational use of subcutaneous tocilizumab in patients with severe COVID-19. Methods: This meta-analysis was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We searched the Cochrane Library, PubMed, Embase, CNKI, SinoMed, and Wanfang Medical Network electronic databases up to 11 January 2023 to identify relevant studies. To obtain the most recent clinical studies of subcutaneous injection of tocilizumab for the treatment of patients with severe COVID-19, we also searched the preprint platforms medRxiv and ChinaXiv. Furthermore, we searched ClinicalTrials.gov for relevant unpublished studies. The studies were screened based on the PICOS principle. The included studies were classified and evaluated for quality based on research type. The RevMan 5.3 software was used to conduct the meta-analysis, and a descriptive analysis was performed to examine relevant outcome indicators. Results: Five observational studies were obtained, involving a total of 498 patients (240 patients in the subcutaneous injection group and 258 patients in the intravenous injection group). All of the studies were of the highest quality. The meta-analysis of the included studies revealed that the mortality rate of patients who received subcutaneous tocilizumab to treat COVID-19 was not significantly higher than that of the intravenous injection group [23.3% (45/193) vs. 18.4% (39/212), RD = 0.06, 95% CI = − 0.01 ~ 0.13, P = 0.11]. Furthermore, there was no significant difference in the proportion of patients requiring mechanical ventilation between the two groups [24.5% (35/143) vs. 22% (35/159), RD = 0.03, 95% CI = − 0.07 ~ 0.12, P = 0.56]. Conclusions: The meta-analyses do not provide evidence that subcutaneous and intravenous tocilizumab formulations for the treatment of severe COVID-19 infection differ regarding their effectiveness. Considering that the meta-analyses cannot replace an appropriately powered non-inferiority study, subcutaneous formulations still need to be used with caution and only when intravenous formulations are in short supply. At present, there is a lack of randomized controlled trials of subcutaneous injection of tocilizumab for the treatment of severe COVID-19, and more clinical research should be conducted. [ABSTRACT FROM AUTHOR]

Objective: Tocilizumab (TCZ) is a recombinant humanized anti-IL-6 receptor monoclonal antibody that is beneficial in critically ill COVID-19 patients. However, the clinical efficacy and safety of immunosuppressants (including tocilizumab, sarilumab and anakinra) in COVID-19 patients are not yet known. These treatments may predispose patients to infection. The aim of this study was to find any connection between the use of tocilizumab and increased secondary bacterial infections. Materials and Methods: In this study, we conducted retrospective analyses of secondary bacterial infections in COVID-19 patients in the intensive care unit. This study included patients with laboratory-confirmed COVID-19 infection or clinically and radiologically confirmed COVID-19 infections who were admitted to the university hospital adult ICUs between March 2020 and January 2022. Demographic data, recent exposure and travel history, clinical symptoms or signs, laboratory findings, and comorbidities were recorded. Microbial cultures from tracheal aspirates, blood, and urine were obtained at admission and throughout the hospital stay. The patients who received tocilizumab treatment noted and analyzed for seconder infections. Blood cultures were taken at least 48 h after the first dose of tocilizumab. Results: We found that 80 patients (%37) had positive culture samples at admission, and most of these cases were admitted to the ICU from various hospital wards. The analyzed data showed that the tocilizumab group had a higher incidence of positive culture samples (%75 vs %35, p=0,0001). The results showed that culture of tocilizumab taken patients had more incidence with metisilin resistance S. aureus, Klebsiella spp., and Acinetobacter spp. (p=0,0001). Infection and mortality rates were much higher than those in the usual care group. Conclusion: Secondary infections and sepsis are major risk factors for mortality. The pathogens detected were drug resistant and had a lower chance of treatment. The benefit of tocilizumab treatment was lost in these patients because of secondary infections. Future studies are needed to help determine the risks of tocilizumab treatments.

Abstract Background We present a rare case of NeuroBehcet’s-related intracranial hypertension without cerebral venous thrombosis (NBrIHwCVT), occurring as the first presentation of NeuroBehcet’s. In addition, we describe the novel use of subcutaneous tocilizumab for this indication. This is followed by a review of the literature on this topic. Case The patient was a 28-year-old lady of Southern Chinese origin with a known history of Behcet’s disease with oral ulcers and ocular findings for which she was on mycophenolate mofetil and adalimumab. She presented with a headache and bilateral disc swelling associated with an intracranial pressure (ICP) of > 40cmH20. There were no structural lesions or cerebral venous thrombosis (CVT) on imaging. Initial lumbar puncture had raised leucocytes and protein. We discuss diagnostic challenges given persistently elevated ICP despite subsequent non-inflammatory cerebrospinal fluid (CSF) profiles and non-response to acetazolamide. She eventually showed a response to immunosuppressant therapy in the form of pulsed methylprednisolone, cyclophosphamide and subsequently subcutaneous tocilizumab, supporting the diagnosis of NBrIHwCVT. Complete normalization of ICP remains challenging. Her disease course was severe, unusual for her ethnicity. Literature review We identified 34 patients (including ours) from 14 publications. We found that the majority of NBrIHwCVT patients were young (average age of 34 years), with a slight female preponderance. Of the 17 cases in the literature with available data on CSF profile, none had raised leucocytes whilst one patient had elevated protein. Patients were generally treated with steroids and occasionally azathioprine, in line with the suspected autoimmune pathophysiology. Of 22 patients with data on outcome, six (27%) were noted to have recurrence of symptoms generally occurring a few months later. Conclusion As demonstrated by this case, NBrIHwCVT can present with BD with raised ICP even if there is no prior history of NB, central Asian ethnicity, cerebral venous thrombosis or features of inflammation on the CSF. We demonstrated how novel use of Tocilizumab may have a role in the management of NBrIHwCVT. Based on our literature review, patients were more likely to be young, female, display a non-inflammatory CSF picture, be treated with steroids and harbour a possibility of recurrence.