Tocilizumab Treatment In Patients Research Articles

Prosthetic infections following tocilizumab treatment in patients with rheumatoid arthritis

Prosthetic infections following tocilizumab treatment in patients with rheumatoid arthritis

Results of tocilizumab treatment in patients with rheumatoid arthritis

The aim of the work was to study the results of tocilizumab (TCZ) treatment in patients with high and moderate activity of rheumatoid arthritis (RA) in addition to basic therapy. The objectives of the work are to assess the degree of RA activity before and after intravenous administration of TCZ using the DAS–28 scale, as well as to compare the effectiveness of TCZ in groups of patients with initially different degrees of activity and the radiological stage of RA. Materials and methods. The study included 58 people with an established diagnosis of RA receiving basic therapy in combination with the biological drug TCZ (India) over the period from 04.2022 to 09.2022. After the consultation decision and the patient informed consent had been obtained, intravenous infusion with a solution of TCZ at the rate of 8 mg/kg was performed once a month for up to 5 courses. Evaluation of the effectiveness of therapy was carried out by analyzing the activity of the disease with the use of DAS-28 scale (including a subjective assessment of pain on a visual analog scale, the number of painful and swollen joints and laboratory indicators of ESR, CRP) before and after each subsequent administration of the drug. Results. The radiological stage of RA correlated with the disease duration (R=0.8). In patients with initial radiological changes, the activity was lower (DAS-28 according to ESR) of RA (p=0.03). High clinical efficacy and safety of TCZ therapy in patients with an initially high and moderate degree of disease activity has been established. In all patients, there was a significant decrease in RA activity according to the DAS-28 scale (according to CRP and ESR) after TCZ injections (p<0.05). Clinical and laboratory remission occurred in 12% of subjects after the second injection, in 44% of patients – after the fourth (significantly more often than after the second injection, p=0.0274), in 37.5% – after the fifth injection of TCZ.

Treatment pattern and changes in oral glucocorticoid dose after tocilizumab treatment in patients with adult Still's disease: An analysis of a Japanese claims database.

Intravenous tocilizumab (TCZ-IV) was approved for the treatment of adult Still's disease (ASD) in Japan in May 2019 based on its efficacy and safety in a phase III randomized controlled trial. This study determined treatment patterns in patients with ASD and assessed oral glucocorticoid (GC) dose changes after TCZ-IV administration in Japanese clinical practice. Patients in the Medical Data Vision database aged 16 years or older with one or more of International Classification of Diseases, 10th revision codes M061 (ASD) or M082 (systemic juvenile idiopathic arthritis) during January 2017-March 2021 (cohort 1) and those initiating TCZ-IV during May 2019-March 2021 (cohort 2) were included. In cohort 1, the proportion of patients who were prescribed interleukin-6 inhibitors (mainly TCZ-IV) increased from 10.8% (January-April 2019 [before TCZ-IV approval]; n = 2002) to 18.3% (January-March 2021 [after TCZ-IV approval]; n = 2008). In cohort 2 (n = 193), 84.5% of patients were on oral GCs (≤5 mg/day: 23.8%) at index date (initial TCZ-IV prescription date); 46/70 (65.7%) were on oral GC at 5 mg/day or higher 12 months after TCZ-IV treatment (primary outcome). After 12 months of treatment, the TCZ-IV retention rate was 73.6% and the TCZ-IV administration interval was every 4 weeks and every 2 weeks in 31.9% and 27.7% of patients, respectively. The use of interleukin-6 inhibitors increased by 7.5% points in Japanese patients with ASD ~2 years after TCZ-IV approval, suggesting that an unmet medical need existed. This study suggests the potential GC-sparing effect of TCZ-IV in patients with ASD in clinical practice.

Outcomes during and after long-term tocilizumab treatment in patients with giant cell arteritis

ObjectiveTo assess outcomes in giant cell arteritis (GCA) patients during and after long-term tocilizumab (TCZ) treatment.MethodsRetrospective analysis of GCA patients treated with TCZ at a single centre (2010–2022). Time to...

Identification of Clinical Response Predictors of Tocilizumab Treatment in Patients with Severe COVID-19 Based on Single-Center Experience

Hyperinflammation in COVID-19 plays a crucial role in pathogenesis and severity; thus, many immunomodulatory agents are applied in its treatment. We aimed to identify good clinical response predictors of tocilizumab (TCZ) treatment in severe COVID-19, among clinical, laboratory, and radiological variables. We conducted a prospective, observational study with 120 patients with severe COVID-19 not improving despite dexamethasone (DEX) treatment. We used parametric and non-parametric statistics, univariate logistic regression, receiver operating characteristic (ROC) curves, and nonlinear factors tertile analysis. In total, 86 (71.7%) patients achieved the primary outcome of a good clinical response to TCZ. We identified forty-nine predictive factors with potential utility in patient selection and treatment monitoring. The strongest included time from symptom onset between 9 and 12 days, less than 70% of estimated radiological lung involvement, and lower activity of lactate dehydrogenase. Additional predictors were associated with respiratory function, vitamin D concentration, comorbidities, and inflammatory/organ damage biomarkers. Adverse events analysis proved the safety of such a regimen. Our study confirmed that using TCZ early in the hyperinflammatory phase, before severe respiratory failure development, is most beneficial. Considering the described predictive factors, employing simple and widely available laboratory, radiological, and clinical tools can optimize patient selection for immunomodulatory treatment with TCZ.

COMPARISON OF EPIDEMIOLOGICAL AND CLINICAL PARAMETERS IN PATIENTS WITH SEVERE COVID 19 TREATED WITH AND WITHOUT TOCILIZUMAB

 Cytokine storm is an uncontrolled immune response in the immunopathogenic mechanism of COVID 19, similar to that of severe influenza. Inflammatory cytokines including: TNF-α, IL-6, IL-8, IL-12, are released in large amounts during of disease progression, causing potential Acute Respiratory Distress Syndrome (ARDS), Hemophagocytic Lymphohistiocytosis (HLH) and Multi-Organ Dysfunction (MOFS). Tocilizumab is an immunosuppressive drug that is used in the treatment of Rheumatoid Arthritis and Systemic Juvenile Idiopathic Arthritis in children. As a human monoclonal antibody targeting Interleukin 6 receptors (IL-6R), it interrupts its action in the cytokine storm and thereby reduces vascular permeability and increased passage of fluid and blood elements into the alveoli that would lead to severe respiratory distress (ARDS). To evaluate the effect of Tocilizumab treatment in patients with severe form of COVID-19. This retrospective study included 213 patients with a severe form of COVID-19 divided into 2 groups: Group 1 of 131 male and female patients who received Cytokine storm is an uncontrolled immune response in the immunopathogenic mechanism of COVID 19, similar to that of severe influenza. Inflammatory cytokines including: TNF-α, IL-6, IL-8, IL-12, are released in large amounts during of disease progression, causing potential Acute Respiratory Distress Syndrome (ARDS), Hemophagocytic Lymphohistiocytosis (HLH) and Multi-Organ Dysfunction (MOFS). Tocilizumab is an immunosuppressive drug that is used in the treatment of Rheumatoid Arthritis and Systemic Juvenile Idiopathic Arthritis in children. As a human monoclonal antibody targeting Interleukin 6 receptors (IL-6R), it interrupts its action in the cytokine storm and thereby reduces vascular permeability and increased passage of fluid and blood elements into the alveoli that would lead to severe respiratory distress (ARDS). To evaluate the effect of Tocilizumab treatment in patients with severe form of COVID-19. This retrospective study included 213 patients with a severe form of COVID-19 divided into 2 groups: Group 1 of 131 male and female patients who received Tocilizumab and Group 2 of 82 male and female patients who did not receive tocilizumab. Patients who received tocilizumab had a significantly shorter stay in the intensive care unit compared to patients who did not received tocilizumab (p=0.021). A significantly lower mortality was registered in patients who were treated with Tocilizumab . This retrospective case control study showed that treatment with Tocilizumab as a human monoclonal antibody in patients with severe form of COVID-19 can lead to shorter hospital stay and reduced mortality compared to patients who did not receive Tocilizumab. Keywords: Cytokine storm, Tocilizumab, COVID 19, Interleukin 6, ARDS.

Long-Term Tocilizumab Treatment in Patients with Rheumatoid Arthritis in Daily Clinical Practice

Long-Term Tocilizumab Treatment in Patients with Rheumatoid Arthritis in Daily Clinical Practice

Therapeutic efficacy, mechanical ventilation, length of hospital stay, and mortality rate in severe COVID-19 patients treated with tocilizumab.

BackgroundThe treatment of severe cases of COVID‐19 disease remains a dilemma so far, because there is no approved therapy for it. This study aimed to estimate the therapeutic efficacy of tocilizumab and its role in reducing the need for mechanical ventilation, length of hospital stay, mortality rate for these cases.MethodThe study included 25 adult patients with confirmed severe COVID‐19 infection. Treatment of all patients followed Egyptian Ministry of Health COVID‐19 protocol in addition to tocilizumab IV (400‐800 mg) as a single dose and then the dose was repeated after at least 12 hours and up to 24 hours from the previous dose. All laboratory and clinical parameters were assessed before and within 24 hours after tocilizumab administration.ResultsAfter receiving TCZ, all patients showed significantly lower median IL 6, LDH, CRP, ferritin , TLC at P < .001, and D‐Dimer at P = .223 than their baseline levels. Also, the number of patients who required mechanical ventilation decreased from 11 to 8. Only five patients died after TCZ treatment. A moderate correlation was found between therapeutic failure and death outcomes and mechanical ventilation need at baseline. The median days of hospitalisation (IQR) were 10 (6‐16).ConclusionTocilizumab treatment in patients with severe COVID‐19 is safe and has significant therapeutic effects and a significant role in the improvement of all laboratory parameters. Also TCZ plays a significant role in the reduction of the length of stay in hospital and ICU, need for mechanical ventilation, and mortality rate.What’s known IL‐6 plays the main role in the acute respiratory distress syndrome (ARDS) associated with severe COVID‐19 infection. Consequently, serum IL‐6 can be considered as an important target in therapeutic management of severe COVID‐19 patients. What’s new Prospective study, carried on 25 adult patients with confirmed severe COVID‐19 infection using tocilizumab, showed significant improvement in their case.Tocilizumab, as an IL‐6 inhibitor, not only lowered IL‐6 level put also showed a significant reduction on median LDH, CRP, ferritin , TLC at P < .001 and D‐Dimer at P = .223 than their baseline levels.Improvement of all laboratory parameters using TCZ was reflected in the reduction of the length of stay in hospital and ICU, need for mechanical ventilation and mortality rate.

Tocilizumab treatment in patients with Schnitzler syndrome: An open-label study

Tocilizumab treatment in patients with Schnitzler syndrome: An open-label study

Real-World 1-Year Retention Rate of Subcutaneous Tocilizumab Treatment in Patients with Moderate to Severe Active Rheumatoid Arthritis: TANDEM Study

IntroductionDrug retention is particularly relevant to assess long-term treatments. This real-world study mainly aimed to describe 1-year retention rate (RR) of subcutaneously administered tocilizumab (TCZ-SC) in patients with moderate to severe active rheumatoid arthritis (RA).MethodsThis non-interventional, prospective, multicenter study (NCT02608112) was conducted in patients with RA initiating TCZ-SC treatment, with an 18-month follow-up. RR was estimated at month 12 in the overall population and baseline subgroups (combination with a conventional synthetic disease-modifying antirheumatic drug (csDMARD) or not, age, body mass index, methotrexate dose), using the Kaplan–Meier method. Patient compliance to TCZ-SC was described using the 5-item Compliance Questionnaire for Rheumatology (CQR5).ResultsAt inclusion 75% of the 285 analyzed patients were women, mean RA duration was 9 ± 9 years, previous RA treatments included biological agents (63%) and/or csDMARDs (94%), mean Disease Activity Score 28 joints-Erythrocyte Sedimentation Rate (DAS28-ESR) was 4.8 ± 1.2. TCZ-SC RR at month 12 was estimated to be 64% (95% CI 58%–69%) with no statistical differences between subgroups. Clinical results improved with TCZ-SC; the proportion of patients treated with combined glucocorticoids decreased from 49% to 22% at month 12. At each follow-up time, at least 80% of patients were high adherers to TCZ-SC (at least 80% of theoretical injections). Among the 286 patients with at least one TCZ-SC injection, 25 patients (9%) experienced serious adverse events related to TCZ-SC with no differences according to patient age.ConclusionsThis real-world study corroborates the RR at month 12 previously shown in interventional studies on TCZ-SC. Our data suggest there are no differences according to patient’s profile (age, BMI), methotrexate doses, and TCZ-SC use.Trial RegistrationNCT02608112.

Increased high molecular weight adiponectin and lean mass during tocilizumab treatment in patients with rheumatoid arthritis: a 12-month multicentre study

BackgroundPatients with rheumatoid arthritis (RA) have an increased risk of cardiovascular (CV) disease. Adiponectin is involved in the metabolism of glucose and lipids with favourable effects on CV disease, especially its high molecular weight (HMW) isoform. Body composition changes are described in RA with various phenotypes including obesity. The effects of tocilizumab on serum adiponectin and body composition, especially fat mass, in patients with RA are not well determined.MethodsPatients with active RA despite previous csDMARDs and/or bDMARDs and who were tocilizumab naïve were enrolled in a multicentre open-label study. They were evaluated at baseline, 1, 3, 6 and 12 months. Clinical assessment included body mass index (BMI) and anthropometric measurements. Lipid and metabolic parameters, serum adiponectin (total and HMW), leptin, resistin and ghrelin were measured at each time point. Body composition (lean mass, fat mass, % fat, fat in the android and gynoid regions) was evaluated at baseline, 6 and 12 months.ResultsOne hundred seven patients were included. Both total and HMW adiponectin significantly increased from baseline to month 3, peaking respectively at month 3 (p = 0.0105) and month 1 (p < 0.0001), then declining progressively until month 6 to 12 and returning to baseline values. Significant elevation in HMW adiponectin persisted at month 6 (p = 0.001). BMI and waist circumference significantly increased at month 6 and 12, as well as lean mass at month 6 (p = 0.0097). Fat mass, percentage fat and android fat did not change over the study period. Lipid parameters (total cholesterol and LDL cholesterol) increased while glycaemia, insulin and HOMA-IR remained stable. Serum leptin, resistin and ghrelin did not change during follow-up.ConclusionsTocilizumab treatment in RA patients was associated with a significant increase in total and HMW adiponectin, especially at the onset of the treatment. Tocilizumab also induced a significant gain in lean mass, while fat mass did not change. These variations in adiponectin levels during tocilizumab treatment could have positive effects on the CV risk of RA patients. In addition, tocilizumab may have an anabolic impact on lean mass/skeletal muscle.Trial registrationThe ADIPRAT study was a phase IV open-label multicentre study retrospectively registered on ClinicalTrials.gov under the number NCT02843789 (date of registration: July 26, 2016).

Subcutaneous tocilizumab treatment in patients with severe COVID-19-related cytokine release syndrome: An observational cohort study.

BackgroundPatients with severe coronavirus disease 2019 (COVID-19) have elevated levels of acute phase reactants and inflammatory cytokines, including interleukin-6, indicative of cytokine release syndrome (CRS). The interleukin-6 receptor inhibitor tocilizumab is used for the treatment of chimeric antigen receptor T-cell therapy–induced CRS.MethodsPatients aged 18 years or older with laboratory-confirmed COVID-19 admitted to the Annunziata Hospital in Cosenza, Italy, through March 7, 2020, who received at least one dose of tocilizumab 162 mg subcutaneously for the treatment of COVID-19–related CRS in addition to standard care were included in this retrospective observational study. The primary observation was the incidence of grade 4 CRS after tocilizumab treatment. Chest computed tomography (CT) scans were evaluated to investigate lung manifestations.FindingsTwelve patients were included; all had fever, cough, and fatigue at presentation, and all had at least one comorbidity (hypertension, six patients; diabetes, five patients; chronic obstructive lung disease, four patients). Seven patients received high-flow nasal cannula oxygen therapy and five received non-invasive mechanical ventilation for lung complications of COVID-19. No incidence of grade 4 CRS was observed within 1 week of tocilizumab administration in all 12 patients (100%) and within 2 days of tocilizumab administration in 5 patients (42%). The predominant pattern on chest CT scans at presentation was ground-glass opacity, air bronchograms, smooth or irregular interlobular or septal thickening, and thickening of the adjacent pleura. Follow-up CT scans 7 to 10 days after tocilizumab treatment showed improvement of lung manifestations in all patients. No adverse events or new safety concerns attributable to tocilizumab were reported.InterpretationTocilizumab administered subcutaneously to patients with COVID-19 and CRS is a promising treatment for reduction in disease activity and improvement in lung function. The effect of tocilizumab should be confirmed in a randomised controlled trial.

Supportive Treatment with Tocilizumab for COVID-19: A Systematic Review

In December of 2019, an outbreak of inexplicable pneumonia cases in several patients appeared in Wuhan, China. What is now known as coronavirus disease 2019 (COVID-19) has spread widely since then and, as of this writing, has infected over 1.8 million people worldwide and has claimed the lives of over 100,000 patients [1]. The disease, COVID-19, is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 has many similarities to SARS-CoV-1 and Middle East respiratory syndrome coronavirus (MERS-CoV), both of which have also been fatal [2]. The number of cases of COVID-19 continues to increase but there is not an approved vaccine or medication that can be used for treatment. Thus, there is an immense need for treatment strategies to help combat this contagious disease. In previous studies, severe patients that have been hospitalized for COVID-19 have had laboratory results that show an increased level of cytokines, specifically interleukin 6 (IL-6) [3]. This increase may be attributed to the cytokine release syndrome (CRS) that is triggered by a variety of factors such as infections [4]. Since IL-6 plays an important role in CRS, it serves as a possible mechanism of treatment in severe patients. Tocilizumab (TCZ) is a recombinant humanized monoclonal antibody that has an antagonist effect on the IL-6 receptor. It is currently used in the treatment of rheumatoid arthritis, but could also play a key role in treatment for severely ill patients with COVID-19. We performed a systematic review to evaluate outcomes associated with TCZ treatment in patients with COVID-19.

Long-term, interventional, open-label extension study evaluating the safety of tocilizumab treatment in patients with polyarticular-course juvenile idiopathic arthritis from Poland and Russia who completed the global, international CHERISH trial

Efficacy and safety of tocilizumab (TCZ), an interleukin-6 receptor inhibitor, were demonstrated in juvenile idiopathic arthritis (JIA) with polyarticular course (pJIA) in the CHERISH trial. This observational, III phase study evaluated long-term treatment of TCZ in pJIA patients was conducted by members of the Pediatric Rheumatology International Trials Organization (PRINTO) from Poland and Russia. Forty-one patients, who had completed the CHERISH core study (104 weeks), were extensionally treated with TCZ (8 mg/kg, intravenous infusion every 4 weeks). Total treatment time was from 131 to 193 weeks. The long-term safety (the primary endpoint) and efficacy were evaluated. All patients achieved ACR70 response in the core study and continued to achieve at least ACR50 response up to week 24 of this study. The safety population comprised 46.41 patient-years (PY). Rates per 100 PY of adverse (AEs) and serious events (SAEs) were 181.0 and 6.46, respectively. Pharyngitis and respiratory tract infections were the most common AEs. Except one AE (severe neutropenia), all others were classified as mild (24.4%) or moderate (29.3%). The incidence of SAEs was low (7.3%). No new safety findings were observed. The safety profile of over 2.5-year treatment with TCZ is consistent with the pre-marketing CHERISH clinical trial. Presented data and continued efficacy response support the use of TCZ in pJIA. EUDRACT No: 2011-001607-12. https://clinicaltrials.gov/ct2/show/study/NCT01575769?term=ML27783

Tocilizumab treatment in patients with rheumatoid arthritis is associated with reduced fibrinogen levels and increased blood loss after total knee arthroplasty

Objective: Since IL-6 has been associated with activation of the coagulation cascade and upregulation of fibrinogen transcription, we retrospectively tested the hypothesis that patients with rheumatoid arthritis (RA) treated with tocilizumab (TCZ) may lose more blood when undergoing total knee arthroplasty (TKA).Methods: This study included 115 RA patients who underwent primary TKA and were preoperatively tested for fibrinogen levels. The blood volume of each patient was calculated using the Nadler formula, and estimated blood loss after TKA was calculated as the change between pre-operative and post-operative hematocrits. If salvaged blood was reinfused, the volume was measured and added to the volume of the estimated blood loss.Results: We observed that patients treated with TCZ had significantly lower pre-operative fibrinogen levels than those not treated with TCZ (190.0 mg/dL versus 347.0 mg/dL, respectively; p = .00018). We also observed a statistically significant increase in mean total volume of estimated blood loss after TKA in RA patients who had been treated with TCZ compared with those not treated with TCZ (797.1 mL versus 511.4 mL, respectively; p = .0039).Conclusion: TCZ treatment in patients with RA may increase the risk of blood loss after TKA because of decreased fibrinogen levels.

Association of disease activity with acute exacerbation of interstitial lung disease during tocilizumab treatment in patients with rheumatoid arthritis: a retrospective, case-control study.

The objective of the study was to identify risk factors for acute exacerbation of interstitial lung disease (ILD) during tocilizumab treatment in patients with rheumatoid arthritis (RA). This is a retrospective, case-control study. We reviewed 395 consecutive RA patients who received tocilizumab. First, we divided the patients according to the presence (RA-ILD) or absence of ILD (non-ILD) assessed by chest X-ray or high-resolution computed tomography, and compared them for characteristics relevant to RA-ILD. Subsequently, focusing on the patients with RA-ILD, we assessed their baseline characteristics and clinical courses comparing patients with acute exacerbation to those without. Comparing 78 with ILD and 317 without ILD, the following were identified as factors related to RA-ILD on multivariate analysis: age 60years or older (OR 4.5, 95% CI 2.2-9.4, P<0.0001), smoking habit (OR 2.9, 95% CI 1.5-5.5, P=0.002), and high rheumatoid factor levels (OR 2.8, 95% CI 1.4-5.5, P=0.002). Of 78 RA-ILD patients, six developed acute exacerbation during tocilizumab treatment. The median duration between the initiation of tocilizumab treatment and the acute exacerbation occurrence was 48weeks. While baseline characteristics did not differ between acute exacerbation and non-acute exacerbation groups, patients experiencing acute exacerbation had significantly higher Clinical Disease Activity Index (CDAI) at 24weeks (20.8 vs. 6.2, P=0.019). Univariate analysis showed that CDAI>10 at 24weeks was a risk factor for acute exacerbation (OR 4.7, 95% CI 2.1-10.4, P=0.02). Uncontrolled arthritis activity during tocilizumab treatment may be associated with acute exacerbation of RA-ILD, suggesting post-treatment monitoring of disease activity is important not only with respect to RA itself but also for RA-ILD.

Peripheral blood CD4(+)CD25(+)CD127(low) regulatory T cells are significantly increased by tocilizumab treatment in patients with rheumatoid arthritis: increase in regulatory T cells correlates with clinical response.

IntroductionTocilizumab (TCZ), an anti-interleukin-6 receptor antibody, is clinically effective against rheumatoid arthritis (RA), and several reports have indicated how TCZ influences a number of mechanisms underlying RA pathogenesis. However, it is still unclear whether TCZ affects inflammatory cells in peripheral blood and whether any such changes are associated with clinical response. We evaluated associations between proportions of subsets of peripheral immune cells and clinical response in patients with RA treated with TCZ.MethodsThirty-nine consecutive patients with RA who started to receive TCZ as their first biologic between March 2010 and April 2012 were enrolled. The proportions of several subsets of peripheral cells with their levels of expression of differentiation markers, activation markers and costimulatory molecules were measured sequentially from baseline to week 52 by flow cytometry analysis.ResultsClinical Disease Activity Index (CDAI) remission was achieved in 53.8% of patients at week 52 of TCZ therapy. The proportions of CD4+CD25+CD127low regulatory T cells (Treg) and HLA-DR+ activated Treg cells significantly increased with TCZ therapy (P < 0.001 and P < 0.001, respectively), whereas proportions of CD3+CD4+CXCR3−CCR6+CD161+ T helper 17 cells did not change over the 52 weeks. The proportions of CD20+CD27+ memory B cells, HLA-DR+CD14+ and CD69+CD14+ activated monocytes, and CD16+CD14+ monocytes significantly decreased (P < 0.001, P < 0.001, P < 0.001 and P < 0.001, respectively). Among them, only the change in Treg cells was inversely correlated with the change in CDAI score (ρ = −0.40, P = 0.011). The most dynamic increase in Treg cells was observed in the CDAI remission group (P < 0.001).ConclusionThis study demonstrates that TCZ affected proportions of circulating immune cells in patients with RA. The proportion of Treg cells among CD4+ cells correlated well with clinical response.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0526-4) contains supplementary material, which is available to authorized users.

Remarkable efficacy of tocilizumab for treating rheumatoid arthritis in patients with high platelet counts

Objectives. To optimize the efficacy of treatment with tocilizumab for rheumatoid arthritis (RA), we comparatively analyzed the outcome of tocilizumab treatment in patients with normal background changes associated closely with IL-6.Patients and Methods. The study involved 87 patients with RA satisfying the diagnostic criteria of the American College of Rheumatology (ACR) and receiving continuous tocilizumab treatment for 24 weeks or longer. The outcome of tocilizumab treatment in these patients was comparatively analyzed in relation to the baseline platelet count (the high platelet count group and the normal group), pretreatment hemoglobin levels (the low group and the normal platelet count group), and speed of bone destruction (the rapid progression group and slow progression group).Results. Treatment with tocilizumab significantly improved the 28-joint disease activity score using the erythrocyte sedimentation rate (DAS28-ESR) and Clinical Disease Activity Index (CDAI), regardless of baseline platelet count, hemoglobin level, or annual speed of bone destruction (ΔTSS). The margins of improvement in DAS28-ESR and CDAI did not differ depending on baseline hemoglobin level or ΔTSS, but the improvement was significantly greater in the high platelet count group than in the normal platelet count group.Conclusions. These results suggest that in patients with high platelet count, IL-6 is a more important factor involved in RA pathogenesis and that tocilizumab is suitable as a first-line biologic for the treatment of RA patients with high platelet count.

Discrepancy Between Clinical and Radiological Responses to Tocilizumab Treatment in Patients with Systemic-onset Juvenile Idiopathic Arthritis

Discrepancy Between Clinical and Radiological Responses to Tocilizumab Treatment in Patients with Systemic-onset Juvenile Idiopathic Arthritis

A56: Macrophage Activation Syndrome in Patients With Systemic Juvenile Idiopathic Arthritis Treated With Tocilizumab

Background/Purpose: Macrophage activation syndrome (MAS) is a severe, potentially fatal complication of systemic juvenile idiopathic arthritis (sJIA).[1] Changes in therapies, including biologics,[2, 3] may trigger MAS. Interleukin-6 (IL-6) plays a major pathogenic role in sJIA; data in animals suggest that high IL-6 levels contribute to the triggering of MAS.[4] Treatment with the IL-6 receptor inhibitor tocilizumab (TCZ) is very effective in patients with sJIA.[2] In this study, we investigated the rates and features of MAS occurring during TCZ treatment in patients with sJIA. Methods: Data were collected from patients with sJIA treated with TCZ in the international phase 3 trial (TENDER), 4 clinical trials in Japan, and the Japanese postmarketing surveillance (JPMS) program. Reported MAS events or disease flares associated with alanine aminotransferase/aspartate aminotransferase (ALT/AST) elevations were collected. Worksheets with event information were assessed by an independent panel (2 pediatric rheumatologists, 1 pediatric hematologist with MAS expertise) overseen by the TENDER lead investigator. Cases were adjudicated as definite MAS, potential MAS, not MAS, or insufficient data. Results: The data set included 112 patients from TENDER (403.0 patient-years' [PY] exposure to TCZ), 149 patients from the Japanese trials (326 PY), and 366 patients from the JPMS program (523.9 PY). Of 31 cases reviewed, 22 events were adjudicated as definite or potential MAS: 5 from TENDER (3 definite, 2 potential), 6 from the Japanese trials (3 definite, 3 potential), and 11 from the JPMS program (5 definite, 6 potential). The rates/100 PY of definite/potential MAS were 1.24 (95% CI, 0.4–2.90) in TENDER, 1.84 (95% CI, 0.68–4.00) in the Japanese trials, and 2.10 (95% CI, 1.05–3.76) in the JPMS program. Features contributing to the adjudication of definite MAS are listed in the 1. All 11 events adjudicated as definite MAS met the preliminary MAS diagnostic guidelines.[6] All definite and potential MAS resolved with the exception of MAS in a patient from the Japanese phase 3 study who died after respiratory/cardiac arrest. Table 1. Criteria for Adjudication of Cases as Definite MAS (n = 11) Features of MAS Patients for Whom These Features Led to Adjudication of Definite MAS n (%)mg a aThresholds for abnormal values were determined according to age and local guidelines. Clinical signs Fever 6 (55) Rash 3 (27) Hemorrhage with purpura, hematuria 2 (18) Hepatomegaly 0 (0) Laboratory featuresa Elevated ALT/AST 11 (100) Thrombocytopenia 9 (82) Elevated ferritin 8 (73) Leukopenia 7 (64) Neutropenia 6 (55) Elevated lactate dehydrogenase 4 (36) Low fibrinogen 4 (36) Increased triglycerides 4 (36) Elevated D-dimers 3 (27) Low hemoglobin 4 (36) Elevated C-reactive protein 2 (18) Low erythrocyte sedimentation rate 2 (18) Conclusion: The use of TCZ does not appear to be associated with increased risk for MAS in sJIA. There were no unusual clinical or laboratory features in these MAS cases.