Tocilizumab Monotherapy Research Articles

Treatment of giant cell arteritis with ultra-short glucocorticoids and tocilizumab: results from the extension of the TOPAZIO study.

To assess the maintenance of efficacy of one year of tocilizumab (TCZ) monotherapy after its discontinuation in large vessel-GCA (LV-GCA). 17 patients with active LV-GCA were previously treated with 3 boluses of intravenous methylprednisone and weekly subcutaneous TCZ in monotherapy for 52 weeks. Patients in relapse-free clinical remission at week 52 discontinued TCZ and entered part two, which was a 26-week observational follow-up period. PET/CT was performed in all patients at the end of the 26-week observational period (week 78). End points were the variation in PET vascular activity score (PETVAS) at week 78 compared with baseline and with week 52, and the proportion of patients with relapse-free clinical remission at week 78 and at the end of the follow-up. Compared with baseline, a significant reduction in PETVAS was observed at week 78, mean (95% CI) change -6.6 (-9.5 to -3.7). However, compared with week 52, PETVAS significantly increase 6 months after TCZ discontinuation (week 78), mean (95% CI) change 4.6 (0.7-8.5). The proportion of patients with relapse-free clinical remission at weeks 78 and at the end of the follow-up (median time from TCZ discontinuation 148 weeks) was 11/17 (65%, 95% CI 38-86) and 8/17 (47%, 95% CI 23-72), respectively. Age and sex-adjusted HR (95% CI) for each unit increase of PETVAS indicating subsequent relapse was 1.36 (0.92-2.00). One year of TCZ monotherapy was effective in maintaining drug-free clinical remission in LV-GCA. Changes in PETVAS early after TCZ discontinuation may predict subsequent relapses. ClinicalTrials.gov, NCT05394909.

Magnetic resonance imaging to monitor disease activity in giant cell arteritis treated with ultra-short glucocorticoids and tocilizumab.

MRI is well established for diagnosing GCA. Its role in monitoring disease activity has yet to be determined. We investigated vascular and musculoskeletal inflammation using MRI in the patients of the GUSTO trial to assess the utility of MRI in monitoring disease activity. Eighteen patients with newly diagnosed GCA received 500 mg methylprednisolone intravenously for 3 consecutive days followed by tocilizumab monotherapy from day 3 until week 52. Cranial, thoracic and abdominal MRI exams were performed at baseline (active, new-onset disease), and at weeks 24, 52 (remission on-treatment), and 104 (remission off-treatment). MRI findings typical for PMR as well as extent and severity of vasculitic disease were rated. In total, 673 vascular segments and 943 musculoskeletal regions in 55 thoracic/abdominal MRI and 490 vascular segments in 49 cranial MRI scans of 18 patients were analysed. Vasculitic vessels were still detectable in one in four cranial segments at week 24. At weeks 52 and 104, no cranial vascular segment showed a vasculitic manifestation. Large vessels, except for the ascending aorta, and PMR displayed little or no decrease in inflammatory findings over time. Vasculitic manifestations in the cranial vessels normalised after 52 weeks of treatment, whereas large vessel and PMR findings persisted despite lasting full remission. The dynamics of cranial vessel signals suggest that MRI of these arteries might qualify as a potential diagnostic tool for monitoring disease activity and for detecting relapse after 52 weeks of treatment.

Dynamics of modified cardiovascular risk factors in patients with rheumatoid arthritis on the background of 5-year therapy with an interleukin 6 receptor inhibitor

The effect of an inhibitor of interleukin (IL) 6 receptors on the state of the cardiovascular system in patients with rheumatoid arthritis (RA) remains poorly understood, especially with its long-term use.The aim – to study the effect of therapy with the IL-6 receptor inhibitor tocilizumab (TCZ) on the dynamics of modifiable risk factors (RF), total cardiovascular risk (CVR), structural changes in the carotid arteries (CA) and the incidence of cardiovascular complications (CVC) in patients with rheumatoid arthritis during the 260-week follow-up period.Material and methods. The study included 37 patients with active RA (32 women and 5 men) with ineffectiveness and/or intolerance to disease modifying anti-rheumatic drugs (DMARDs); median age was 56 [48; 68] years, disease duration was 92 [49; 158] months; DAS28 (Disease Activity Score 28) – 6.2 [5.5; 6.7] points; all patients were seropositive for rheumatoid factor (RF), 86% – for antibodies to cyclic citrullinated peptide (ACCP). Patients received TCZ therapy 8 mg/kg intravenously every 4 weeks; after 192 [176; 210] weeks, 60% of patients switched to subcutaneous administration of the drug at a dose of 162 mg once a week. In 51% of patients with RA, TCZ monotherapy was performed, in 49% – combination therapy of TCZ with DMARDs. Statins were received by 17 (46%) patients, including 7 patients before and 10 after inclusion in the study. All patients underwent an assessment of traditional risk factors, the total cardiovascular risk was calculated using the mSCORE scale, atherosclerotic vascular lesions were assessed by the detection of atherosclerotic plaques (ASP) of CA. The observation period was 260.4 [251.5; 283.4] weeks.Results. After 260 weeks of TCZ therapy, RA remission was observed in 32 (86%) patients, low activity – in 5 (14%) patients. During the observation period, the frequency of modified RF and the total CVR did not change significantly, an increase in body mass index (BMI) by 11% was recorded, the number of patients with hypercholesterolemia and a reduced level of HDL cholesterol (C) decreased. In patients without statin therapy, there were no significant changes in the blood lipid spectrum. In the group of patients receiving statins, there was an increase in HDL-C by 43%, a decrease in cholesterol levels by 15%, atherogenic index (AI) by 56% (p<0.01 in all cases) and associations between the dynamics of ∆cholesterol and ∆CRP (r=0.35; p=0.04), ∆LDL-C and ∆CRP (r=0.41; p=0.03). Significant structural changes in CA in RA patients by the end of 260 weeks of TCZ therapy were not identified. Initially, intima-media thickness (IMT) CA positively moderately correlated with age (r=0.7; p<0.01), BMI (r=0.37; p<0.01), systolic blood pressure (SBP) (r=0.62; p<0.01) and weakly with lipid spectrum parameters – cholesterol (r=0.29; p<0.01), LDL-C (r=0.36; p<0.01). No new associations of IMT CA by the end of the observation, as well as the relationship of the IMT CA value with the indicators of RA activity and the ongoing therapy, were identified. By the end of the study, the distribution of patients by mSCORE value and CVR level did not change significantly. The incidence of CVC was 0,54 per 100 patient-years over a 260-week period of TCZ use. Conclusion. Against the background of long-term TCZ therapy in RA patients, there was no increase in CVR and significant structural changes in CA. It is necessary to dynamically monitor the blood lipid profile and CVR in RA patients receiving TCZ therapy. Statin therapy can successfully control dyslipidemia in RA patients who receive long-term TCZ.

Tocilizumab Reduces Depression Risk in Rheumatoid Arthritis Patients: A Systematic Review and Meta-Analysis.

Depression is a possible cause of the increased mental health risks associated with rheumatoid arthritis (RA), including depression-related complications. Biological disease-modifying antirheumatic drug (bDMARDs) therapies have emerged as innovative anti-inflammatory drugs with positive effects on mental well-being. Tocilizumab is a bDMARDs commonly used to treat RA and its influence on depression needs to be studied. It targets interleukin-6 (IL-6) receptors, reducing inflammation, which may also alleviate depressive symptoms due to the role of inflammation in the pathophysiology of depression. Thus, its influence on depression needs to be studied. To assess the strength of the association between exposure to tocilizumab and the rate of development of depression in patients with RA and to evaluate tocilizumab as an exposure and depression as an outcome in these patients, a search was conducted in the MEDLINE, PreMEDLINE, Cochrane, and Scopus databases from January 1980 to April 2024. Inclusion criteria were studies that diagnosed RA according to the latest American College of Rheumatology/European League Against Rheumatism guidelines or a rheumatologist and provided information on tocilizumab exposure and diagnosed depression as an outcome. The present meta-analysis was conducted following the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. These studies were assessed for eligibility by the author and an independent assessor. To summarize the findings, the meta-analysis combined the relative risk estimates from each study with raw data counts. Twelve studies in the meta-analysis fulfilled the inclusion criteria. Tocilizumab monotherapy exhibited a promising beneficial effect on the risk of depression, indicated by the decreased risk in RA patients (Relative risk 0.68, 95% CI 0.20, 2.31). Patients with RA on tocilizumab treatment had a lower risk of developing depression compared to those unexposed to tocilizumab treatment. Therefore, future longitudinal studies are needed to confirm the beneficial effect of tocilizumab on depression in the RA population.

Comparison of biologic monotherapy versus biologic and disease-modifying anti-rheumatic drug combination in the treatment of non-systemic juvenile idiopathic arthritis

Purpose To explore the efficacy of biologics as mono- or combination therapy with conventional disease modifying anti-rheumatic drugs (cDMARDs) in the treatment of juvenile idiopathic arthritis (JIA). Material and Methods Medical records of patients with JIA followed-up from January 2020 to 2023 who were treated either with biologic drugs as monotherapy or with combination of cDMARD were reviewed retrospectively. Data of demographic features, clinical scores and treatments were assessed. Results Two hundred five cases received etanercept, adalimumab, or tocilizumab alone or in combination with a cDMARD for JIA were included. The male to female ratio of the cohort was almost equal. Oligoarticular was the most common subtype of JIA. Majority (n=128, 62.4%) of the group received biologic drugs as monotherapy, while the remaining third (n=77, 37.6%) used a combination of biologic and a cDMARD. Nearly half of the group (57.1%) were treated with etanercept and etanercept monotherapy was the most commonly used one among all JIA subtypes except juvenile psoriatic arthritis. Adalimumab combination therapy was prescribed in most of the children with juvenile psoriatic arthritis. Adalimumab, alone or in combination with methotrexate, was preferred for all 8 patients with uveitis at the onset of the disease. Adalimumab combined (n=9) and tocilizumab monotherapy (n=4) were the most common biologics in those who developed uveitis during follow-up. Conclusion Etanercept, adalimumab, or tocilizumab are effective and safe biologics in treatment of JIA. Considering their cost-effective properties, choosing biologic drugs timely as combined or monotherapy is effective in preventing early and late sequelae of JIA.

Lights and shadows on the efficacy of tocilizumab monotherapy in large vessel giant cell arteritis.

Lights and shadows on the efficacy of tocilizumab monotherapy in large vessel giant cell arteritis.

Serum proteomics in giant cell arteritis in response to a three-day pulse of glucocorticoid followed by tocilizumab monotherapy (the GUSTO trial).

Proteome analyses in patients with newly diagnosed, untreated giant cell arteritis (GCA) have not been reported previously, nor are changes of protein expression upon treatment with glucocorticoids (GC) and/or tocilizumab (TCZ) known. The GUSTO trial allows to address these questions, provides the opportunity to learn about the differential effects of GC and TCZ on proteomics and may help to identify serum proteins to monitor disease activity. Serum samples obtained from 16 patients with new-onset GCA at different time points (day 0, 3, 10, and week 4, 24, 52) during the GUSTO trial (NCT03745586) were examined for 1436 differentially expressed proteins (DEPs) based on proximity extension assay technology. The patients received 500 mg methylprednisolone intravenously for 3 consecutive days followed by TCZ monotherapy. When comparing day 0 (before the first GC infusion) with week 52 (lasting remission), 434 DEPs (213↑, 221↓) were identified. In response to treatment, the majority of changes occurred within 10 days. GC inversely regulated 25 proteins compared to remission. No difference was observed between weeks 24 and 52 during established remission and ongoing TCZ treatment. Expression of CCL7, MMP12, and CXCL9 was not regulated by IL6. Disease-regulated serum proteins improved within 10 days and were normalized within 24 weeks, showing a kinetic corresponding to the gradual achievement of clinical remission. The proteins inversely regulated by GC and TCZ shed light on the differential effects of the two drugs. CCL7, CXCL9, and MMP12 are biomarkers that reflect disease activity despite normalized C-reactive protein levels.

OA31 Real life experience of tocilizumab treatment for giant cell arteritis

Abstract Background/Aims Giant cell arteritis (GCA) has been revolutionised by fast track pathways that ensure early secure diagnosis. The GiACTA study provided evidence for the beneficial role of tocilizumab in the treatment of GCA and encouraged us all to reconsider the role of corticosteroids. These data relate to real life experience of the use of tocilizumab, including current status of patients after completing the initial year of treatment. In Scotland, tocilizumab was initially used for patients with relapsing disease or steroid complications. However, since 2018, the Scottish Medicines Consortium has supported use from disease onset and it has become increasingly common to consider adding at diagnosis. Methods The case notes of 23 patients treated with tocilizumab were reviewed back to 2017. Patient demographics were collated including whether cranial (C) or large vessel vasculitis (LVV) variant. The diagnosis of GCA had to be confirmed by biopsy or imaging with GCA rheumatology clinic review. Any patients who discontinued tocilizumab prior to completing one year had the reason recorded. Duration on tocilizumab was intended to be one year. Data were reviewed to capture outcomes after treatment was withdrawn. Results 2 patients with non-relapsing disease discontinued tocilizumab within the first month due to early relative neutropenia (1.4). 5 of 21 patients who completed treatment have since had additional tocilizumab treatment. 1 patient with particularly severe relapsing disease and steroid complications remains on long term tapered tocilizumab monotherapy without attempt to stop (C and LVV). 4 patients (LVV=C) flared within 1-9 months (median 6 months) and resumed with steroids and subsequent tapers; all had commenced for relapsing disease. 1 patient (C), commenced on tocilizumab at diagnosis, opted for MTX when flared. 15 remaining patients are on no steroid, methotrexate or tocilizumab and are free of disease activity as yet, but undergoing monitoring for flare (12C 3 LVV variant). Conclusion Tocilizumab is effective, limits steroid exposure and is well-tolerated by patients. The most common reason for discontinuing tocilizumab was relative neutropenia (neutrophils 1-1.4). The majority of patients discontinued tocilizumab and have not yet flared off all treatment. Cranial variant was less associated with relapse after tocilizumab treatment versus LVV. New diagnoses appear less prone to relapse off tocilizumab than patients already known to have relapsing disease prior to using tocilizumab. Patients discontinuing tocilizumab benefit from ongoing monitoring to recognise the early stages of returning disease; this would need to be provided for at least one year. Patients discontinuing treatment, their GPs and carers need advice on routes to escalate concerns about returning symptoms. Fast track services need to provide a flare service in addition to a diagnosis pathway if there is to be safety, confidence and expert support for this patient group and primary care colleagues. Disclosure L.M.M. Hutton: Other; 2022 Roche educational grant to attend BSR.

Efficacy and safety of selective JAK 1 inhibitor filgotinib in active rheumatoid arthritis patients with inadequate response to methotrexate: comparative study with filgotinib and tocilizumab examined by clinical index as well as musculoskeletal ultrasound assessment (TRANSFORM study): study protocol for a randomized, open-label, parallel-group, multicenter, and non-inferiority clinical trial

BackgroundAdministration of Janus kinase (JAK) inhibitors and biological disease-modifying antirheumatic drugs has dramatically improved even the clinical outcomes in patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX). Dysregulation of JAK-STAT pathways via overproduction of cytokines, such as interleukin-6, is involved in the pathogenesis of RA. Filgotinib is a selective JAK1 inhibitor pending approval for use in RA. By inhibition of the JAK-STAT pathway, filgotinib is effective in suppressing disease activity and preventing the progression of joint destruction. Similarly, interleukin-6 inhibitors such as tocilizumab also inhibit the JAK-STAT pathways by inhibition of interleukin-6 signaling. We present the protocol for a study that will evaluate whether the effectiveness of filgotinib monotherapy is non-inferior to that of tocilizumab monotherapy in RA patients with an inadequate response to MTX.MethodsThis study is an interventional, multicenter, randomized, open-label, parallel-group, and non-inferiority clinical trial with a 52-week follow-up. Study participants will be 400 RA patients with at least moderate disease activity during treatment with MTX. Participants will be randomized in a 1:1 ratio to administer filgotinib monotherapy or subcutaneous tocilizumab monotherapy switched from MTX. We will evaluate disease activity by measuring clinical disease activity indices and by using musculoskeletal ultrasound (MSUS). The primary endpoint is the proportion of patients who achieve an American College of Rheumatology 50 response at week 12. Secondary endpoints are changes from baseline in the MSUS scores. We will also comprehensively analyze serum levels of multiple biomarkers, such as cytokines and chemokines.DiscussionThe study results are expected to show the non-inferiority of the effectiveness of filgotinib monotherapy to that of tocilizumab monotherapy in RA patients with inadequate response to MTX. The strength of this study is its prospective evaluation of therapeutic efficacy using not only clinical disease activity indices, but also MSUS, which accurately and objectively evaluates disease activity at the joint level among patients drawn from multiple centers with a standardized evaluation by MSUS. We will evaluate the effectiveness of both drugs by integrating multilateral assessments—clinical disease activity indices, MSUS findings, and serum biomarkers.Trial registrationJapan Registry of Clinical Trials (https://jrct.niph.go.jp) jRCTs071200107. Registered on March 3, 2021. ClinicalTrials.gov NCT05090410. Registered on October 22, 2021.

Pilot study of tocilizumab monotherapy for active chronic periaortitis

ObjectivesTo investigate the effectiveness and safety of TCZ (tocilizumab) monotherapy for chronic periaortitis (CP) patients at acute active stage.MethodsTwelve patients with definite or possible diagnosis of CP were enrolled and...

Effectiveness and safety of tocilizumab in monotherapy in biologic-naïve and non-naïve patients with rheumatoid arthritis in a real-world setting

ObjectiveTo evaluate the effectiveness and safety of tocilizumab (TCZ) monotherapy in biologic-naïve patients with rheumatoid arthritis (RA) versus patients with previous biologic exposure in a real-world setting. Materials and methodsNon-controlled clinical-trial, 32-week prospective multicenter study including RA patients with moderate-severe disease activity starting TCZ in monotherapy who had a prior inadequate response or were intolerant to methotrexate (MTX). Effectiveness according to EULAR response evaluated at 24-week and safety at 32-weekwere assessed. ResultsOf the 93 were enrolled of whom 84 (90%) were eligible for the effectiveness analysis. Biologic-naïve patients (n=46, 54.8%) were younger (51.5 versus 57.9) with shorter disease duration (6.4 versus 13.3) but presented similar comorbidities in comparison with non-naïve patients. DAS28 remission was achieved in a higher percentage in the group of patients with prior biological treatment. 89 adverse events (AE) were recorded in 50 patients, most of them non-serious AE (non-SAE) (86.3%). ConclusionsIn a real world setting, TCZ exhibit similar effectiveness and safety in monotherapy in patients with RA regardless previous exposure to other biologic therapies. This study provides additional and valuable real-world findings on the use of TCZ in patients with RA.

Giant cell arteritis successfully treated with subcutaneous tocilizumab monotherapy.

Glucocorticoid remains the mainstay for treatment of large vessel vasculitis (LVV) including giant cell arteritis (GCA); however, the disease affects the elderly for whom the adverse effects of glucocorticoid are problematic. Recently, some reports have suggested that intravenous tocilizumab (TCZ) monotherapy is effective for this disease. To date, it remains unknown whether subcutaneous TCZ monotherapy is also effective. Here, we present a first case of GCA successfully treated with subcutaneous TCZ monotherapy. A 75-year-old woman presented with shoulder and hip pain. She was diagnosed with polymyalgia rheumatica (PMR) and treated with low-dose prednisolone (15mg daily); however, she discontinued glucocorticoid therapy at her discretion due to the psychiatric adverse effect (cognitive dysfunction). Seven months later, her shoulder and hip pain relapsed. Furthermore, 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) revealed uptake in the descending thoracic aorta, indicating a complication of LVV. She refused to take glucocorticoid for fear of psychiatric adverse effects and chose subcutaneous TCZ monotherapy (162mg weekly) for treating this life-threatening urgent condition. Nine months later, her shoulder and hip pain resolved and FDG-PET/CT demonstrated no uptake in the descending thoracic aorta, indicating a successful treatment with subcutaneous TCZ monotherapy for the disease. No adverse events and disease relapse were found during observation period. Our case and the literature review suggest that not only intravenous injection but also subcutaneous injection of TCZ monotherapy can serve as an alternative treatment for patients with GCA who have comorbidities or refuse to take glucocorticoid.

Divergent regulatory T cell responses to high-dose methylprednisolone and tocilizumab in giant cell arteritis

• The clinical data of the proof-of-concept-study about tocilizumab (TCZ) monotherapy after ultra-short glucocorticoid (GC) administration in giant cell arteritis (GCA) was published in The Lancet Rheumatology ( https://doi.org/10.1016/S2665-9913(21)00152-1 ). • In this manuscript we summarize and analyze the T cell data of the mentioned study: • This is the first study analyzing circulating regulatory T cells in newly diagnosed GCA cases prior to GC administration. • The study design allowed a comparative analysis of T cell responses to GCs and TCZ. • The data suggests a different type of regulatory T cells being involved in control of disease.

Harmonization of Public Coverage Policies for Biologic Drugs in the Treatment of Rheumatoid Arthritis


 For rheumatoid arthritis (RA), treatment guidelines and clinical evidence support the combination (either dual or triple) of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) before accessing a biologic DMARD (bDMARD). Federal, provincial, and territorial (FPT) drug plans currently have different coverage criteria for bDMARD eligibility in RA. To align their criteria, these plans should consider the inclusion of at least 1 line of combination csDMARDs before a bDMARD:
 
 For dual csDMARDs: Saskatchewan, Veterans Affairs Canada, and Canadian Armed Forces would need to change their current coverage criteria to include at least 1 line of dual csDMARDs before access to a bDMARD.
 For triple csDMARDs: Alberta, Saskatchewan, Manitoba, Veterans Affairs Canada, and Canadian Armed Forces would need to alter their current coverage criteria because each of these FPT drug plans only consider csDMARD monotherapy or dual csDMARDs in their current coverage criteria.
 
 
 Most FPT drug plans require a failure of at least 2 lines to 3 lines of csDMARD therapy before a bDMARD, except British Columbia, Ontario, Newfoundland and Labrador, Veterans Affairs Canada, and Canadian Armed Forces, which offer an option to access bDMARDs after 1 line of combination csDMARDs. British Columbia, Ontario, the Atlantic provinces, Yukon, Correctional Service of Canada, and Non-Insured Health Benefits include triple csDMARDs in their coverage criteria. Alberta, Manitoba, Veterans Affairs Canada, and Canadian Armed Forces include dual, but not triple, csDMARDs in their criteria; however, Veterans Affairs Canada and Canadian Armed Forces do not require a trial of dual csDMARDs if 2 lines of csDMARD monotherapy have been attempted. Saskatchewan is the only jurisdiction that only requires csDMARD monotherapy. Canadian private insurers have also reached a consensus to implement a trial requirement of dual csDMARDs before a bDMARD across their formularies.
 Evidence-based guidelines, including the 2012 Canadian Rheumatology Association guidelines, recommend csDMARD monotherapy (methotrexate [MTX] is preferred unless contraindicated) as first-line treatment for RA, although a guideline published in 2018 by the Brazilian Society of Rheumatology stated that combination therapy with 2 or more csDMARDs may also be used as a first-line treatment. These guidelines generally recommend combination csDMARDs after csDMARD monotherapy is deemed ineffective.
 A network meta-analysis found that triple csDMARDs is more efficacious than dual csDMARDs, etanercept monotherapy, and 4 mg/kg tocilizumab monotherapy and comparable to other bDMARDs (alone or in combination with MTX), targeted synthetic DMARDs in combination with MTX, and biosimilars in combination with MTX. Additionally, economic evidence demonstrated that triple csDMARDs is more cost-effective than etanercept plus MTX combination therapy.
 Time to first bDMARD was, on average, longer in Alberta, British Columbia, and Ontario than in Saskatchewan, Manitoba, and the Atlantic provinces by approximately 4 months, which may be partially explained by differences in coverage criteria for the number of prior lines of csDMARD therapy required. Increasing the time to initiating a bDMARD could lead to budget savings without impacting clinical outcomes.

Efficacy of Tocilizumab Monotherapy Versus Tocilizumab and Methotrexate Combination Therapy in the Prevention of Radiographic Progression in Rheumatoid Arthritis: An Analysis Using Individual Patient Data From Multiple Clinical Trials

ObjectiveTo compare the effects of preventing radiographic progression (in its 3 components) of tocilizumab (TCZ) monotherapy with those of TCZ and methotrexate (MTX) in combination therapy (TCZ + MTX), and to evaluate possible effect modifiers in this model.MethodsRandomized trials that compared TCZ monotherapy to TCZ + MTX combination therapy for differences in radiographic progression were analyzed on an individual patient data level using mixed‐effects models, and data were collected from 820 subjects with either early rheumatoid arthritis (RA) or established RA. Outcomes were classified as the absence of radiographic progression after 2 years (i.e., preventing radiographic progression) as measured by total Sharp/van der Heijde score (SHS), erosion score, and joint space narrowing (JSN) score. Effect modification by baseline joint damage, disease duration, and Disease Activity Score in 28 joints (DAS28) was studied.ResultsOverall, TCZ + MTX combination therapy was more effective in preventing radiographic progression compared to TCZ monotherapy, which was measured by total SHS score. However, in patients with early RA who had more joint damage compared to those with less joint damage at baseline (relative risk [RR] 1.02 versus RR 0.91, respectively) or in patients with a lower DAS28 score compared to those with a higher DAS28 score (RR 1.04 versus RR 0.92, respectively) at baseline, this advantage disappeared. In patients with established RA, the advantage of TCZ + MTX versus TCZ alone in the prevention of radiographic progression disappeared with a longer disease duration at baseline (RR 1.04 versus 0.83). Results of erosion scores as an outcome were in line with these findings, though findings for JSN scores were less clear.ConclusionCombination therapy with TCZ + MTX is more effective in preventing radiographic progression compared to TCZ monotherapy, but the effectiveness of TCZ monotherapy may approximate the effectiveness of TCZ + MTX in patients with early RA who have more joint damage and/or a lower DAS28 at baseline and in patients with established RA who have longer disease duration.

Experience With the Use of Baricitinib and Tocilizumab Monotherapy or Combined, in Patients With Interstitial Pneumonia Secondary to Coronavirus COVID19: A Real-World Study

ObjectiveTo describe the experience of treatment with baricitinib (BARI) and/or tocilizumab (TCZ), in monotherapy or combined, in patients admitted for interstitial pneumonia secondary to COVID19, and for 30 days after discharge. MethodsMedical records of patients admitted with COVID19 and IP with PaO2/FiO2<300, treated with BARI and/or TCZ, and compared with patients who did not, were retrospectively reviewed. ResultsSixty patients were included; 43 (72%) are males, mean age 67 (SD: 14) years (<50 years: 17%; 51–70: 30%; >70: 53%), with 8.5 (SD: 1) days of symptoms. Sixteen (27%) patients required ICU (94% in <70 years). Fifteen (25%) patients died, 67% in >70 years; 11 (18%) patients died in the first 15 days of admission and 4 (7%) between days 16 to 30. Twenty-three (38%) patients received BARI, 12 (52%) monotherapy (Group 1), during 6 (SD: 2.6) days on average, none required ICU and 2 (17%) died. Thirty-one (52%) patients received TCZ, 20 (33%) as monotherapy (Group 2), 16 (52%) patients required ICU and 4 (20%) died. In the 11 (18%) patients who received BARI (2.8 [SD: 2.5] days average) and TCZ combined (Group 3), 3 (27%) required ICU and died. There were no severe side effects in BARI or TCZ patients. In the 17 (28%) patients who received neither BARI nor TCZ (Group 4), none required ICU and 6 (35%) died. Mean (SD) PaO2/FiO2 at admission between groups was respectively: 167 (82.3), 221 (114.9), 236 (82.3), 276 (83.2). ConclusionTreatment with BARI and TCZ did not cause serious side effects. They could be considered early in patients with NI secondary to COVID19 and impaired PaO2/PaFi.

Problems to Consider Before Determining the Regimen of the Treatment for Juvenile Systemic Sclerosis Treatment: A Case Report Where Tocilizumab Monotherapy Succeeded Efficiently and Safely.

Juvenile systemic sclerosis (SSc) is a rare condition that results in various disorders, including growth retardation and learning disabilities in addition to impaired quality of life due to fibrosis and microvascular disorders in multiple organs. Recently, efficacies of immunosuppressants such as cyclophosphamide and mycophenolate mofetil, as well as biological agents, have been reported in adult patients with SSc. However, there has been no consensus in the treatment of juvenile SSc due to its rarity and the fact that skin sclerosis may be self-limiting in some patients. Here, we present a case of 13-year-onset SSc with growth retardation and learning disabilities, in addition to skin sclerosis, interstitial lung disease, and possible myocardial fibrosis that was successfully treated with tocilizumab monotherapy without remarkable adverse reactions. As careful case-by-case management of patient’s growth and education along with standard treatment is needed, the documentation of such case is important for the evaluation of the efficient and safe therapy for juvenile SSc.

DYNAMICS OF TRADITIONAL MODIFIABLE RISK FACTORS, TOTAL CARDIOVASCULAR RISK IN PATIENTS WITH RHEUMATOID ARTHRITIS ON LONG-TERM IL-6 RECEPTOR ANTAGONIST TREATMENT

TOPIC: Cardiovascular Disease TYPE: Original Investigations PURPOSE: The effect of an inhibitor of interleukin (IL)-6 receptors on the state of the cardiovascular system in patients (pts) with rheumatoid arthritis (RA) remains poorly understood.Objective: To study the effect of therapy with an inhibitor of IL-6 receptors, tocilizumab (TCZ), on the dynamics of modifiable risk factors (RF), total cardiovascular risk in RA pts during a 12-month (m) follow-up period. METHODS: The study included 40 pts with active RA (33 women/7 men) with ineffectiveness and/or intolerance to basic anti-inflammatory drugs (DMARDs); the median age was 55[49;64]years, the duration of the disease — 102[48;162]m; DAS28 6.2[5.5;6.7]points; all pts were seropositive for rheumatoid factor, 80% for antibodies to cyclic citrullinated peptide. Pts received TCZ 8mg/kg therapy every 4 weeks: 52% received TCZ monotherapy, 48% received combined TCZ therapy with DMARDs. All pts underwent an assessment of traditional RF and were determined plasma total cholesterol (TC), HDL-C, LDL-C, and triglyceride (TG) levels. The total cardiovascular risk was calculated using the mSCORE. RESULTS: After 12m of TCZ therapy, a decrease in disease activity was noted: remission was observed in 64% (n=25) of pts, low disease activity - in 31% (n=12). DAS28, HAQ, CRP and ESR concentrations decreased significantly. ? high frequency of traditional RF was found in RA pts: dyslipidemia - 67%, arterial hypertension - 65%, overweight - 55%, burdened heredity for cardiovascular diseases - 35%, smoking - 15%. Every third pts had a combination of three or more traditional RF. After 12 m of TCZ therapy, the frequency of traditional RF did not significantly change, there was an increase in BMI by 2%, an increase in the concentration of HDL-C in serum by 27%, a decrease in the atherogenic index (IA) by 28% (p<0.01). Moreover, an increase in the level of HDL-C by the finish was found in pts regardless of statin therapy. Changes in the concentration of other lipids during the observation, including during therapy with statins, were not observed. A negative correlation the dynamics of the levels of ?TC and ?CRP (R=−0,37, p<0.05), ? LDL-C and ?CRP (R=−0,42, p<0.01) was found. A very high cardiovascular risk according to the SCORE scale was determined in 78% of pts, moderate - in 2%, and low - in 20% of pts. The distribution of pts by mSCORE value and level of cardiovascular risk were not documented after 12m of TCZ therapy. CONCLUSIONS: After 12 m of TCZ therapy resulted in decreased RA activity, increased the level of HDL-C, IA, BMI; the frequency of traditional RF and the total cardiovascular risk did not change. Despite the very high risk of developing CVD associated with the inflammatory activity of RA, the accumulation of traditional RF and their combination. Insufficient effectiveness of statin therapy was revealed. CLINICAL IMPLICATIONS: cardiovascular risk, rheumatoid arthritis, therapy with an inhibitor of IL-6 receptors DISCLOSURES: No relevant relationships by Elena Gerasimova, source=Web Response No relevant relationships by Yulia Gorbunova, source=Web Response No relevant relationships by Alexandra Martynova, source=Web Response No relevant relationships by Tatiana Popkova, source=Web Response

Prompt Reduction in CRP, IL-6, IFN-γ, IP-10, and MCP-1 and a Relatively Low Basal Ratio of Ferritin/CRP Is Possibly Associated With the Efficacy of Tocilizumab Monotherapy in Severely to Critically Ill Patients With COVID-19.

Background and Aim: Tocilizumab, a humanized anti-IL-6 receptor antibody, has been used to treat severely to critically ill patients with COVID-19. A living systematic review with meta-analysis of recent RCTs indicates that the combination therapy of corticosteroids and tocilizumab produce better outcomes, while previous observational studies suggest that tocilizumab monotherapy is beneficial for substantial numbers of patients. However, what patients could respond to tocilizumab monotherapy remained unknown.Methods: In this retrospective study we evaluated the effects of tocilizumab monotherapy on the clinical characteristics, serum biomediator levels, viral elimination, and specific IgG antibody induction in 13 severely to critically ill patients and compared with those of dexamethasone monotherapy and dexamethasone plus tocilizumab.Results: A single tocilizumab administration led to a rapid improvement in clinical characteristics, inflammatory findings, and oxygen supply in 7 of 11 patients with severe COVID-19, and could recover from mechanical ventilation management (MVM) in 2 patients with critically ill COVID-19. Four patients exhibited rapidly worsening even after tocilizumab administration and required MVM and additional methylprednisolone treatment. Tocilizumab did not delay viral elimination or inhibit IgG production specific for the virus, whereas dexamethasone inhibited IgG induction. A multiplex cytokine array system revealed a significant increase in the serum expression of 54 out of 80 biomediators in patients with COVID-19 compared with that in healthy controls. Compared with those who promptly recovered in response to tocilizumab, patients requiring MVM showed a significantly higher ratio of basal level of ferritin/CRP and a persistent increase in the levels of CRP and specific cytokines and chemokines including IL-6, IFN-γ, IP-10, and MCP-1. The basal high ratio of ferritin/CRP was also associated with clinical deterioration even in patients treated with dexamethasone and tocilizumab.Conclusion: Tocilizumab as monotherapy has substantial beneficial effects in some patients with severe COVID-19, who showed a relatively low level of the ratio of ferritin/CRP and prompt reduction in CRP, IL-6, IFN-γ, IP-10, and MCP-1. The high ratio of ferritin/CRP is associated with rapid worsening of pneumonia. Further evaluation is warranted to clarify whether tocilizumab monotherapy or its combination with corticosteroid is preferred for severely to critically ill patients with COVID-19.

Retrospective analysis of anti-inflammatory therapies during the first wave of COVID-19 at a community hospital.

BACKGROUNDOur understanding of the severe acute respiratory syndrome coronavirus 2 has evolved since the first reported cases in December 2019, and a greater emphasis has been placed on the hyper-inflammatory response in severely ill patients. The purpose of this study was to determine risk factors for mortality and the impact of anti-inflammatory therapies on survival.AIMTo determine the impact of various therapies on outcomes in severe coronavirus disease 2019 patients with a focus on anti-inflammatory and immune-modulating agents.METHODSA retrospective analysis was conducted on 261 patients admitted or transferred to the intensive care unit in two community hospitals between March 12, 2020 and June 17, 2020. Totally 167 patients received glucocorticoid (GC) therapy. Seventy-three patients received GC alone, 94 received GC and tocilizumab, 28 received tocilizumab monotherapy, and 66 received no anti-inflammatory therapy.RESULTSPatient survival was associated with GC use, either alone or with tocilizumab, and decreased vasopressor requirements. Delayed administration of GC was found to decrease the survival benefit of GC therapy. No difference in survival was found with varying anticoagulant doses, convalescent plasma, tocilizumab monotherapy; prone ventilation, hydroxychloroquine, azithromycin, or intravenous ascorbic acid use.CONCLUSIONThis analysis demonstrated the survival benefit associated with anti-inflammatory therapy of GC, with or without tocilizumab, with the combination providing the most benefit. More studies are needed to assess the optimal timing of anti-inflammatory therapy initiation.