Tocilizumab Therapy Research Articles

Tocilizumab for Advanced Non‐Small‐Cell Lung Cancer With Concomitant Cachexia: An Observational Study

ABSTRACTBackgroundCancer cachexia significantly contributes to morbidity and mortality in patients with non‐small‐cell lung cancer (NSCLC). Inflammatory pathways mediated by interleukin‐6 (IL‐6) play a crucial role in the development of cancer cachexia. This study aimed to investigate the use of tocilizumab in the management of NSCLC with coexisting IL‐6‐elevated cachexia.MethodsIn this retrospective study, data were collected from patients with NSCLC and concurrent IL‐6‐elevated cachexia who received either tocilizumab plus antitumour therapy or antitumour therapy alone. The primary endpoints were overall survival (OS) and improved modified Glasgow Prognostic Score (mGPS) at Week 12. The secondary endpoints included changes from baseline over 12 weeks in body weight, albumin, C‐reactive protein (CRP) and mGPS. Qualitative improvements in patient self‐rated appetite and fatigue were reported as exploratory analysis.ResultsThe study included 49 patients diagnosed with NSCLC and IL‐6‐elevated cachexia, Eastern Cooperative Oncology Group performance status of 2–4. Of these, 26 received tocilizumab in combination with antitumour therapy, and 23 received antitumour therapy alone. The majority of these patients were male (87.8%). Baseline characteristics were almost identical between the two groups. The tocilizumab group demonstrated a significantly longer median OS compared to the control group (15.1 vs. 3.2 months; hazard ratio 0.18, 95% confidence interval 0.08–0.38; p < 0.001). The rate of patients surviving with mGPS improvement at Week 12 was significantly higher in the tocilizumab group than in the control group (risk difference 0.88, 95% confidence interval 0.75–1.00; p < 0.001). Over the 12‐week period, significant improvements were observed in body weight, albumin, CRP and mGPS in the tocilizumab group compared to the control group (body weight: 5.15 ± 0.53 kg vs. −5.69 ± 0.76 kg, p = 0.041; albumin: 5.89 ± 0.70 g/L vs. −2.97 ± 0.71 g/L, p < 0.001; CRP: −91.50 ± 7.15 mg/L vs. 9.47 ± 13.69 mg/L, p < 0.001; mGPS: −1.61 ± 0.15 vs. 0.03 ± 0.08, p < 0.001). The tocilizumab group also displayed significantly higher rates of improvement in appetite and fatigue (both p < 0.001). The incidence of Grade 3 or higher adverse events was 34.6% in the tocilizumab group compared to 78.3% in the control group. Tocilizumab‐related adverse events were observed in three patients (11.5%), including two cases of neutropenia and one case of skin and subcutaneous tissue infection.ConclusionTocilizumab demonstrated significant benefits in survival and various clinical parameters, including body weight, albumin, CRP, mGPS and symptom burden in patients with NSCLC and concurrent IL‐6‐elevated cachexia. Given the existing unmet medical need for effective interventions for cancer cachexia, tocilizumab may be considered as a potential treatment option.

Multiscale, mechanistic model of Rheumatoid Arthritis to enable decision making in late stage drug development

Rheumatoid Arthritis (RA) is a chronic autoimmune inflammatory disease that affects about 0.1% to 2% of the population worldwide. Despite the development of several novel therapies, there is only limited benefit for many patients. Thus, there is room for new approaches to improve response to therapy, including designing better trials e.g., by identifying subpopulations that can benefit from specific classes of therapy and enabling reverse translation by analyzing completed clinical trials. We have developed an open-source, mechanistic multi-scale model of RA, which captures the interactions of key immune cells and mediators in an inflamed joint. The model consists of a treatment-naive Virtual Population (Vpop) that responds appropriately (i.e. as reported in clinical trials) to standard-of-care treatment options—Methotrexate (MTX) and Adalimumab (ADA, anti-TNF-α) and an MTX inadequate responder sub-population that responds appropriately to Tocilizumab (TCZ, anti-IL-6R) therapy. The clinical read-outs of interest are the American College of Rheumatology score (ACR score) and Disease Activity Score (DAS28-CRP), which is modeled to be dependent on the physiological variables in the model. Further, we have validated the Vpop by predicting the therapy response of TCZ on ADA Non-responders. This paper aims to share our approach, equations, and code to enable community evaluation and greater adoption of mechanistic models in drug development for autoimmune diseases.

Successful resolution of refractory cystoid macular edema following tocilizumab therapy in a case of severe recalcitrant juvenile idiopathic arthritis-associated uveitis

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children, with JIA-associated uveitis being the most frequent extra-articular manifestation. If inadequately treated, JIA-associated uveitis can lead to persistent macular edema, potentially causing blinding complications. Tocilizumab, a humanized monoclonal antibody against IL-6, binds to its receptors and inhibits the pro-inflammatory effects of IL-6. This study reports the case of a 30-year-old female with polyarticular JIA-associated uveitis for 24 years, suffering from bilateral refractory cystoid macular edema (CME) resistant to treatments such as corticosteroids, methotrexate, infliximab, adalimumab, and tofacitinib. She received an intravitreal dexamethasone implant in her right eye. Remission of JIA and resolution of CME were achieved with tocilizumab 162 mg subcutaneous injections, combined with low-dose corticosteroids. After 12 doses of tocilizumab, there was no evidence of active uveitis in either eye.

Secondary amyloidosis treated with tocilizumab as a complication of temporal arteritis

Background: Temporal arteritis is a large-vessel vasculitis mostly seen in the elderly. Amyloidosis may be secondary to a chronic inflammation of body organs. Here, we present the second case report of temporal arteritis complicated by amyloidosis that was successfully treated by tocilizumab. Case presentation: A 64-year-old female presented complaining of fatigue, fever, and diarrhea accompanied by abdominal pain. One year before presentation, she was diagnosed with temporal arteritis. She was treated with 15 mg/day oral prednisone for the last 6 months, with partial remission, but persistence of the fatigue and an elevated erythrocyte sedimentation rate (ESR, 56 mm/h). Physical examination showed tenderness of both temporal arteries and a soft abdomen. Colon tissue biopsy showed amyloid depositions in the vessels and stroma that were positive for Congo red staining. Tocilizumab was started with 8 mg/kg intravenous, the diarrhea resolved, and the arthralgia improved within 1 month, with a decrease in the ESR to 8 mm/h, and a C-reactive protein (CRP) level of 0.98 mg/dl. Monthly tocilizumab therapy remains efficacious 12 months later and was stopped due to lack of tocilizumab from the hospital. No side effects of tocilizumab were registered. Conclusion: Chronic inflammation may be complicated by amyloidosis in patients with rheumatic diseases and genetic predisposition. Therefore, it is important to screen for intestinal Amyloid A (AA) amyloidosis in individuals with gastrointestinal disorders complicated by rheumatic disorders. AA amyloidosis may be complicated by temporal arteritis and presented with gastrointestinal symptoms such as diarrhea.

COMPARATIVE EFFICACY OF METHYLPREDNISOLONE AND TOCILIZUMAB IN PATIENTS WITH A SEVERE FORM OF COVID-19

Background. Recently, we have again noted an increase in the incidence of COVID-19. The treatment of patients with severe coronavirus infection poses a significant medical challenge. Objectives. The purpose of this research was to compare the efficacy of standard therapy and pulses of methylprednisolone in combination with or without tocilizumab in patients with a severe form of COVID-19. Patients and methods. In a retrospective study, the medical charts of 220 patients with a severe course of COVID-19 were reviewed. Patients were divided into four groups: those on daily methylprednisolone at a dose of 32 mg enterally; patients who received methylprednisolone pulses (500 mg daily intravenously for three consecutive days, with a subsequent change to the 32 mg of methylprednisolone daily); patients who received a single dose of 400 mg tocilizumab in combination with a 32 mg of methylprednisolone daily; patients who received a single dose of 400 mg tocilizumab in combination with methyl­prednisolone pulse therapy. At the end of therapy, 28-day mortality and the number of intubations in each group one week after the end of therapy were analyzed. Results. Patients treated with a combination of tocilizumab and pulse methylprednisolone therapy had the lowest risk of death (p<0.001), OR=0.03 (95 % CI 0.01-0.16), compared to patients treated only with 32 mg of methylprednisolone. Conclusions. Methylprednisolone pulses therapy is more effective than therapy with methylprednisolone at a daily dose of 32 mg. The combination of methylprednisolone and tocilizumab is more effective than the isolated administration of methylprednisolone. The combination of tocilizumab with methylprednisolone pulse therapy had the highest therapeutic effect.

Clinical outcomes of tocilizumab therapy in polyarticular and systemic juvenile idiopathic arthritis: a single-center analysis (2018-2022)

AbstractThis single-center retrospective study aimed to evaluate the safety and efficacy of Tocilizumab (TOC) in children with polyarticular (pJIA) and systemic juvenile idiopathic arthritis (sJIA) who exhibited inadequate responses to disease-modifying antirheumatic drugs (DMARDs) and biological modifiers (bDMARDs). Conducted at the Department of Pediatric Rheumatology, National Institute of Geriatrics, Rheumatology, and Rehabilitation in Warsaw, Poland, between 2018 and 2022, the study enrolled 29 patients diagnosed with JIA based on International League of Associations for Rheumatology (ILAR) criteria. The cohort comprised 13 sJIA and 16 pJIA patients, aged 2-18 years, receiving TOC treatment for 24 months. Safety and efficacy assessments included analysis of medical documentation, laboratory tests (CRP, ESR, WBC), and Juvenile Disease Activity Score (JADAS) 71 at baseline, 3, 6, 12, and 24 months post-treatment initiation. Significant reductions in CRP and ESR levels were observed within three months, with sustained improvement in JADAS71 scores over the 24-month treatment period. A substantial majority, 73.07% of patients, achieved inactive disease status or low disease activity, highlighting T0C’s effectiveness. Adverse effects were manageable, predominantly involving mild to moderate infections, with no serious adverse events or instances of macrophage activation syndrome (MAS). The study also noted a steroid-sparing effect of TOC, with a reduction in glucocorticoid usage among the cohort. Tocilizumab demonstrates substantial efficacy in reducing disease activity and improving clinical outcomes in patients with pJIA and sJIA, coupled with a favorable safety profile. These findings reinforce the role of TOC as a critical component of the therapeutic arsenal for JIA, offering hope for improved quality of life and disease management in this patient population.

The Effects of Different Treatment Methods on Blood Hematological Parameters İn COVID 19: A Retrospective Look at Patients in Pandemic İntensive Care Unit During The First Wave of the Pandemic

Introduction: In this study, we compared the pre- and post-treatment values of basic hematological parameters in severe COVID 19 patients, whose were received favipiravir, tocilizumab, methylprednisolone and convalescent plasma therapy. Methods: Hematological parameters such as eosinophyl, neutrophil, lymphocyte, platelet count and, neutrophil / lymphocyte, platelet/ lymphocyte ratio were investigated pre and post treatment of favipiravir, tocilizumab convalescent plasma and methylprednisolone in severe COVID 19 patients in ICU. Results: Lymphocyt values were increased after convelescent plasma theraphy and i.v. methyl prednisolon group. Eosinophil count improvement was only in the favipiravir group . We found that favipiravir, convalescent plasma andmethyl prednisolon treatment, were statistically significant increased both NLR and PLR. Conclusion : Hematologic parameters and their contribution of the respond of the treatment and clinical improvement should be taken into account.

Use of Tocilizumab in the treatment of chronic active antibody-mediated rejection in pediatric kidney transplant recipients

Chronic active antibody-mediated rejection is one of the leading causes of graft failure and traditional therapies have unclear efficacy. Recent studies suggested that Tocilizumab could stabilize renal function and improve microvascular inflammation. Here we report the outcomes of Tocilizumab therapy in 6 pediatric kidney transplant recipients with biopsy-proven chronic active antibody-mediated rejection resistant to standard treatments. All patients received monthly Tocilizumab infusions for 6 months and were monitored for renal function (creatinine, estimated glomerular filtration rate (eGFR), proteinuria) and Human Leukocyte Antigens (HLA) and non-HLA antibodies at baseline and 3 and 6 months after Tocilizumab initiation. For each patient, a follow-up biopsy was scheduled at the end of the treatment. Renal function did not show stabilization or improvement (mean eGFR 37 ml/min/1.73 m2 pre-Tocilizumab and 27 ml/min/1.73 m2 3 months after-Tocilizumab) and proteinuria remained stable. Moreover, Tocilizumab had no impact on HLA and non-HLA antibodies. Graft loss was observed in 3 patients (50 %) and 4 patients who underwent post-treatment biopsy showed a worsening in overall chronicity scores. In our pediatric series, rescue therapy with Tocilizumab did not appear to be effective in modifying the natural history of chronic active antibody-mediated rejection.

Correlation Between Brixia Score Imaging and Clinical Laboratory Results In Severe-Critical Covid-19 Patients Receiving Standard Therapy Compared To Tocilizumab

Background. Coronavirus infection disease 19 (COVID-19) is a global health issue. Brixia score and inflammatory markers can assess COVID-19 severity. Severe-critical phase becomes the main concern of clinicians in the management of COVID-19 to reduce mortality. Standard therapy for moderate to severe COVID-19 is convalescent plasma which functions as an antiviral and immunomodulator, while tocilizumab is an IL-6 antagonist which underlies the occurrence of cytokine storms in severe-critical COVID-19. Aims. To examine the correlation between the Brixia score and clinical laboratory results in patients with severe-critical degree of Covid-19 who received both standard therapy and tocilizumab Method. A retrospective cohort study of Brixia score, with clinical laboratory results of D-dimer, fibrinogen, ferritin, and CRP (C-reactive protein) COVID-19 patients with severe-critical phase who were administered standard therapy and tocilizumab who were treated at RSUP DR Kariadi Semarang, then a correlation was carried out between the Brixia score and clinical laboratory results using a correlation test Spearman. Results. The research data consisted of 72 subjects divided into groups that were adiminstered tocilizumab therapy (36 subjects) and standard therapy (36 subjects). There was a significant correlation between the Brixia score and the D-dimer result with p = 0.024 (p <0.05), correlation coefficient = 0.377 in the standard pre-therapy and post therapy. A p-value of less than 0.05 indicates no significant correlation between the Brixia score and clinical laboratory results before or after tocilizumab therapy. Conclusion. There is a significant correlation between the Brixia score results and the D-dimer results in COVID-19 patients who are adiministered standard therapy, but not significant correlation in tocilizumab

Serum GM-CSF level is a predictor of treatment response to tocilizumab in rheumatoid arthritis patients: a prospective observational cohort study

BackgroundThe 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).MethodsActive 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.ResultsDisease 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.ConclusionThe 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.

Novel germline STAT3 gain-of-function mutation causes autoimmune diseases and severe growth failure

In recent years, germline gain-of-function (GOF) mutations in signal transducer and activator of transcription 3 (STAT3) have been identified as a cause of early-onset multiorgan autoimmune diseases with the widespread use of next-generation sequencing, and targeted therapies such as tocilizumab have been reported to be effective. We sought to assess whether a novel STAT3 mutation detected by whole-exome sequencing is pathogenic and examine the efficacy of targeted therapy. A pediatric patient with idiopathic pulmonary hemosiderosis, autoimmune thyroiditis, inflammatory bowel disease unclassified, leukocytosis, thrombocytosis, and severe growth failure was examined. This 7-year-old boy had idiopathic pulmonary hemosiderosis at the age of 6 months. Despite high-dose steroid therapy, pulmonary fibrosis progressed. Furthermore, he presented with severe growth failure, autoimmune thyroiditis, leukocytosis, thrombocytosis, and inflammation bowel disease unclassified. Given the presence of multiple autoimmune diseases, whole-exome sequencing was performed, which detected germline de novo heterozygous STAT3 mutation (NM_139276.2; c.2144C>A, p.(P715Q)). Dual-luciferase reporter assay revealed this novel STAT3 mutation as GOF. After starting tocilizumab therapy at the age of 6, hospital stays decreased, and the progression of pulmonary fibrosis was decelerated without increasing the steroid dose. New autoimmune diseases did not develop, and no apparent adverse effects on growth have been observed. Tocilizumab may be effective for patients with STAT3 GOF mutation, including those requiring long-term management of idiopathic pulmonary hemosiderosis. Diagnosis of patients with early-onset multiorgan autoimmune diseases in which STAT3 GOF is suspected should be confirmed by genetic testing and functional analysis to consider the introduction of targeted therapies.

Cytokine release syndrome triggered by programmed death 1 blockade (sintilimab) therapy in a psoriasis patient: A case report

BACKGROUND In recent years, immune checkpoint inhibitors (ICIs) have demonstrated remarkable efficacy across diverse malignancies. Notably, in patients with advanced gastric cancer, the use of programmed death 1 (PD-1) blockade has significantly prolonged overall survival, marking a pivotal advancement comparable to the impact of Herceptin over the past two decades. While the therapeutic benefits of ICIs are evident, the increasing use of immunotherapy has led to an increase in immune-related adverse events. CASE SUMMARY This article presents the case of a patient with advanced gastric cancer and chronic plaque psoriasis. Following sintilimab therapy, the patient developed severe rashes accompanied by cytokine release syndrome (CRS). Fortunately, effective management was achieved through the administration of glucocorticoid, tocilizumab, and acitretin, which resulted in favorable outcomes. CONCLUSION Glucocorticoid and tocilizumab therapy was effective in managing CRS after PD-1 blockade therapy for gastric cancer in a patient with chronic plaque psoriasis.

Medication use evaluation of tocilizumab implementation in COVID-19 treatment guidelines: A causal inference approach.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Introduction of new medications to health-system formularies is often not accompanied by assessments of their clinical impact on the local patient population. The growing availability of electronic health record (EHR) data and advancements in pharmacoepidemiology methods offer institutions the opportunity to monitor the medication implementation process and assess clinical effectiveness in the local clinical context. In this study, we applied novel causal inference methods to evaluate the effects of a formulary policy introducing tocilizumab therapy for critically ill patients with coronavirus disease 2019 (COVID-19). We conducted a medication use evaluation utilizing EHR data from patients admitted to a large medical center during the 6 months before and after implementation of a formulary policy endorsing the use of tocilizumab for treatment of COVID-19. The impact of tocilizumab on 28-day all-cause mortality was assessed using a difference-in-differences analysis, with ineligible patients serving as a nonequivalent control group, and a matched analysis guided by a target trial emulation framework. Safety endpoints assessed included the incidence of secondary infections and liver enzyme elevations. Our findings were benchmarked against clinical trials, an observational study, and a meta-analysis. Following guideline modification, tocilizumab was administered to 69% of eligible patients. This implementation was associated with a 3.1% absolute risk reduction in 28-day mortality (odds ratio, 0.86; number needed to treat to prevent one death, 32) attributable to the inclusion of tocilizumab in the guidelines and an additional 8.6% absolute risk reduction (odds ratio, 0.65; number needed to treat to prevent one death, 12) linked to its administration. These findings were consistent with estimates from published literature, although the effect estimates from the difference-in-differences analysis exhibited imprecision. Evaluating formulary management decisions through novel causal inference approaches offers valuable estimates of clinical effectiveness and the potential to optimize the impact of new medications on population outcomes.

Tocilizumab for advanced non-small cell lung cancer with concomitant inflammatory cachexia: A single-centre study.

2647 Background: Cancer cachexia significantly contributes to morbidity and mortality in patients with non-small cell lung cancer (NSCLC). Inflammatory pathways mediated by interleukin-6 play a crucial role in the development of cancer cachexia. This study aimed to investigate the use of tocilizumab, an anti-interleukin-6 receptor inhibitor, in the management of NSCLC with coexisting inflammatory cachexia. Methods: Data were collected from patients with NSCLC and concurrent inflammatory cachexia who received either tocilizumab plus anti-tumour therapy or anti-tumour therapy alone. The primary endpoints were overall survival (OS) and improved modified Glasgow Prognostic Score (mGPS) at week 12, while secondary endpoints included changes from baseline over 12 weeks in body weight, albumin, C-reactive protein and mGPS. Qualitative improvements in patient self-rated appetite and fatigue were reported as exploratory analysis. Results: The study included 49 patients diagnosed with NSCLC and coexisting inflammatory cachexia, of which 26 received tocilizumab in combination with anti-tumour therapy, and 23 received anti-tumour therapy alone. The tocilizumab group demonstrated a significantly longer median OS compared to the control group (15.1 vs. 3.2 months; hazard ratio 0.18, 95% confidence interval 0.08-0.38; p < 0.001). The rate of patients surviving with mGPS improvement at week 12 was significantly higher in the tocilizumab group than in the control group (OR 168.7, 95% CI 16.3-1746.5; p < 0.001). Over the 12-week period, significant improvements were observed in body weight, albumin, C-reactive protein, and mGPS in the tocilizumab group compared to the control group. Additionally, the tocilizumab group displayed significantly higher rates of improvement in appetite and fatigue. The incidence of grade 3 or higher adverse events was 34.6% in the tocilizumab group compared to 78.3% in the control group. Tocilizumab-related adverse events were observed in three patients (11.5%), including two cases of neutropenia and one case of skin and subcutaneous tissue infection. Conclusions: Tocilizumab demonstrated significant benefits in survival and various clinical parameters, including body weight, albumin, C-reactive protein, mGPS, and symptom burden in patients with NSCLC and concurrent inflammatory cachexia. Given the existing unmet medical need for effective interventions for cancer cachexia, tocilizumab may be considered as a potential treatment option.

Effectiveness Of Tocilizumab In Aortitis And Aneurysms Associated With Giant Cell Arteritis

ObjectiveAortitis in Giant Cell Arteritis (GCA-aortitis) is a frequent complication that may lead to aneurysms. Tocilizumab (TCZ) was approved in GCA, but the efficacy in GCA-aortitis and aneurysms has not been analyzed to date. Our aim was to assess the effectiveness and safety of TCZ in a wide series of GCA-aortitis and aneurysms. MethodsMulticentre observational study with GCA-aortitis treated with TCZ. GCA was diagnosed by: a) ACR criteria, b) temporal artery biopsy, and/or c) imaging techniques. Aortitis was diagnosed mainly by PET/CT. Main outcomes were EULAR and imaging remission. Others were clinical remission, analytical normalization, corticosteroid-sparing effect, and the prevention and improvement of aneurysms. Results196 patients with GCA-aortitis treated with TCZ. After 6 months, 72.2% reached EULAR remission but only 12% an imaging remission; increasing up-to 81.4% and 31.8%, respectively, at 24 months. A rapid clinical remission, ESR and CRP normalization was observed in 47.4%, 84.3% and 55.6%, at 1 month, increasing to 89.6%, 85.3% and 80.3% at 24 months, respectively.Aneurysms were present in 10 (5%) patients. Five of them required early surgery, while 3 others enlarged. No patient on TCZ therapy developed aneurysms during follow-up. ConclusionIn patients with GCA-aortitis treated with TCZ, a rapid and maintained clinical and analytical improvement was observed. However, there was an uncoupling between clinical and EULAR remission with imaging remission.

#3105 Tocilizumab for treatment of antibody mediated rejection in kidney transplant patients

Abstract Background and Aims Chronic active antibody-mediated rejection (caABMR) causes 40% of long-term graft failure after kidney transplantation (KT). Early treatment is of great importance, however, hard clinical evidence is still lacking. Currently the combination of plasmapheresis (PF), rituximab and intravenous immunoglobulin is used as standard treatment. Tocilizumab (TCZ) is a monoclonal antibody, IL-6 receptor antagonist, and it inhibits the production of donor-specific antibodies (DSA). We hypothesized that tocilizumab administration has an additional effect on graft survival and non-inferior to standard therapy in KT patients with ABMR. Method Retrospective single-center noninferiority case-control study was performed by involving 73 KT patients (43.5 ± 14.3 years, females 31, eGFR 19.5 ± 13.4) with biopsy proven ABMR diagnosed between June 2017 and May 2022. 19 patients received 8 mg/kg intravenous TCZ therapy for 6 months (12 aABMR, 7 caABMR, 38.6 ± 12.8 years, females 6). In the control group (C, n=54, 10 aABMR, 44 caABMR, 45.2 ± 14.5 years, females 25), 20 patients received plasmapheresis treatment, the rest stayed on optimized maintenance therapy (tacrolimus, mycophenolic acid, prednisolone). Baseline demographic data, standard laboratory data, proteinuria and DSA level were also monitored and analyzed. Results Graft loss occurred in 13 cases (6 aABMR, 7 caABMR) in KT on TCZ therapy and 43 (6 aABMR, 37 caABMR) in C group, meaning significantly lower risk of graft loss in the TCZ group (RR 0.69, p=0.036) during the median follow-up of 11.3 (IQR 2.5-23.1) months. In TCZ group, all caABMR patients lost their graft during the observation. In TCZ group, 1 year after the TCZ treatment, DSA (pooled) was lower (7028 (575-17782) versus 1605 (551-16903), p<0.05). Conclusion Early administration of TCZ seems to be noninferior to standard therapy and effective to prevent early graft loss as part of standard therapy in aABMR. Further clinical studies are needed to clarify clinical indications of TCZ and its long-term effects on the course of chronic active ABMR.

Anticytokine Therapy and Corticosteroids for Cytokine Release Syndrome and for Neurotoxicity Following T-Cell Engager or CAR T-Cell Therapy

What Is the Issue? Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are the most common toxicities secondary to T-cell engager or chimeric antigen receptor (CAR) T-cell therapy. The US FDA and Health Canada approved tocilizumab, an anti-interleukin-6 receptor antagonist, for the management of severe or life-threatening cases of CRS. Corticosteroids also play an important role in CRS management and are the mainstay of ICANS management. Decision-makers are interested in understanding the use of anticytokine drugs (i.e., tocilizumab, anakinra, siltuximab) and/or corticosteroids in the management of CRS and ICANS following T-cell engager or CAR T-cell therapy. What Did We Do? We identified and summarized the literature comparing the clinical effectiveness and safety of anticytokine therapy and/or corticosteroids with alternative care or treatment as usual for treating and preventing of CRS and ICANS. We also searched for evidence-based recommendations for the use of anticytokine therapy and/or corticosteroids to treat and prevent CRS and ICANS. A research information specialist conducted a literature search of peer-reviewed and grey literature sources published between January 1, 2019 and February 26, 2024 for CRS; and between January 1, 2019 and March 4, 2024 for ICANS. One reviewer screened citations for inclusion based on predefined criteria, critically appraised the included studies, and narratively summarized the findings. What Did We Find? This report presents evidence-based findings on 3 retrospective chart review studies, 2 prospective cohort studies, and 4 consensus guidelines. Limited and low-quality clinical evidence from studies with a high risk of bias suggested that early use of tocilizumab or corticosteroids, or prophylactic use of tocilizumab or anakinra may reduce the risk of a high-grade CRS without a negative impact on neurotoxicity or immunotherapy treatment outcomes. The included guidelines recommend the use of tocilizumab for treatment of higher-grade CRS, or for treatment of grade 1 CRS if symptoms persist for 3 days or more. Corticosteroids could be added in conjunction if there is no improvement or persistent symptoms after tocilizumab therapy. For the management of ICANS in the absence of concurrent CRS, supportive care is the preferred treatment option for grade 1 ICANS, while corticosteroids are recommended for the management of grade 2 to 4 ICANS. In the presence of concurrent CRS, guidelines recommend tocilizumab therapy as per management of CRS, and corticosteroids should be continued until improvement to grade 1. We did not identify any clinical evidence regarding the clinical efficacy and safety of anticytokine therapy and/or corticosteroids for treatment of CRS and ICANS compared with alternative treatment or treatment as usual. We also did not identify any guidelines for the use of prophylactic anticytokine therapy, corticosteroids, or both for the prevention of CRS and ICANS. What Does This Mean? Despite limited and low-quality evidence, the findings suggest some potential benefits of prophylactic or early use of anticytokine therapy and corticosteroids for the management of immunotherapy-related toxicities. Guidelines offer guidance on the management of CRS, ICANS and other less common toxicities related to immunotherapy based on the available low-quality evidence. When using the clinical evidence and recommendations summarized in this report to inform decisions, decision-makers should consider that the evidence is limited and of low quality. To improve the certainty of findings, there is a need for more robust prospective clinical trials with larger sample sizes, and lower risk of bias.

Changes in metabolic parameters and serum YKL-40 levels in Chinese rheumatoid arthritis patients during tocilizumab therapy.

To investigate the metabolic changes during therapy of tocilizumab (TCZ) and methotrexate (MTX) in non-diabetic rheumatoid arthritis (RA) patients and for the first time explore the associations between metabolic parameters and serum YKL-40 (sYKL-40) levels. We enrolled active non-diabetic RA patients who were refractory to MTX. Patients received intravenous TCZ (8mg/kg) once every 4weeks combined with MTX for 24weeks. Metabolic parameters and sYKL-40 levels were measured before TCZ infusion at baseline, week 4, week 12, and week 24. Correlations were assessed by the Spearman's rank correlation analysis. A total of 91 non-diabetic RA patients were enrolled in this study. At week 24, we observed a significant elevation in body mass index (BMI), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) levels. In contrast, there was a significant decrease in TC/HDL‑C ratio. No apparent changes in insulin resistance were found. Additionally, we detected a significant reduction in sYKL-40 levels during the study. At week 24, changes in sYKL-40 levels showed a significant negative correlation (r = -0.334, p = 0.002) with changes in TC levels. The combined therapy of TCZ and MTX resulted in a significant increase in BMI and lipid levels, while an evident decrease in the TC/HDL‑C ratio and sYKL-40 levels in RA patients. Additionally, there was a significant correlation between the decrease in sYKL-40 levels and the increase in TC levels during treatment with TCZ and MTX. Key Points • Lipid levels elevated significantly and sYKL-40 levels decreased obviously after therapy of TCZ combined with MTX in Chinese RA patients. • There was a significant correlation between the increase in TC levels and the decrease in sYKL-40 levels during treatment with TCZ and MTX in RA patients.

Efficacy and safety of an early response-based tapering regimen of tocilizumab in children with systemic juvenile idiopathic arthritis.

Systemic juvenile idiopathic arthritis (sJIA) is a distinct disease subset, with a poorer prognosis compared with other JIA subsets. Tocilizumab has an important role in the management of sJIA refractory to standard initial therapy. However, no specific guidelines exist for the tapering of tocilizumab therapy in sJIA, which could have implications on the overall cost and side effects of treatment. This was an observational study which included 21 children with refractory sJIA, who were initially put on injection tocilizumab every 2 weekly, with subsequent dosing tapered to 4 weekly and 6 weekly intervals based on JIA ACR 70 responses at 12 and 24 weeks, respectively. The primary outcome at week 36 included JIA ACR 30, 50, 70, and 90 response rates with other efficacy and safety measures as secondary outcomes. At 36 weeks, JIA ACR 30, 50, 70, and 90 responses were observed in 90.5%, 90.5%, 71.4%, and 52.4% patients respectively along with significant improvement in hematological and inflammatory parameters. The mean prednisolone dose could be reduced from 0.54 to 0.13 mg/kg/day and around 29% patients were able to discontinue steroids altogether. No serious adverse events were recorded. With drug tapering, we could curtail on 26% of the total tocilizumab dose that would have been otherwise required on the continuous 2 weekly protocol. Tocilizumab, used in an early response-based tapering regimen, was both safe and efficacious in children with sJIA refractory to standard therapy. Larger and longer duration studies are required to further validate our observations.

Long-term clinicopathological characteristics of TAFRO syndrome and its relapse: a case series study.

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. 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. 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. 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.