The systemic score may identify life-threatening evolution in Still's disease: data from the GIRRCS AOSD-study group and the AIDA Network Still's Disease Registry.

OBJECTIVES: To evaluate the clinical usefulness of the systemic score in the prediction of life-threatening evolution in Still's disease. To assess the clinical relevance of each component of the systemic score in predicting life-threatening evolution and to derive patient subsets accordingly. METHODS: A multicenter, observational, prospective study was designed including patients included in the GIRRCS (Gruppo Italiano Di Ricerca in Reumatologia Clinica e Sperimentale) AOSD-study group and AIDA (AutoInflammatory Disease Alliance) Network Still's Disease Registry. Patients were assessed if variables to derive the systemic score were available. The life-threatening evolution was defined as mortality, whichever the clinical course, and/or macrophage activation syndrome (MAS), a secondary hemophagocytic lymphohistiocytosis associated with a poor prognosis. RESULTS: Totally 597 patients with Still's disease were assessed (age 36.6±17.3 years; male 44.4%). The systemic score, assessed as continuous variable, significantly predicted the life-threatening evolution (OR: 1.24, 95%CI:1.07-1.42; p=0.004). A systemic score ≥7 also significantly predicted the likelihood of a patient experiencing life-threatening evolution (OR: 3.36, 95%CI:1.81-6.25; p<0.001). Assessing the clinical relevance of each component of the systemic score, liver involvement (OR: 1.68, 95%CI:1.48-2.67; p=0.031) and lung disease (OR: 2.12, 95%CI:1.14-4.49; p=0.042) both significantly predicted life-threatening evolution. The clinical characteristics of patients with liver involvement and lung disease were derived, highlighting their relevance in multiorgan disease manifestations. CONCLUSION: The clinical utility of the systemic score was shown in identifying Still's disease at higher risk of life-threatening evolution in a large cohort. Furthermore, the clinical relevance of liver involvement and lung disease was highlighted.

Secukinumab is not associated with cancer recurrence or progression in patients with spondyloarthritis and history of neoplastic disease.

Secukinumab is a monoclonal antibody directed against interleukin-17 approved for the treatment of psoriasis and spondyloarthritis. The favorable oncological profile of secukinumab in patients with a history of malignancy has been shown in patients with psoriasis. However, systematic data to this regard have not been published yet for patients with spondyloarthritis. The objective of the present study was to evaluate the oncological safety of secukinumab in patients affected by this group of diseases. We performed a retrospective study in which we identified from our cohort patients with spondyloarthritis treated with secukinumab and with a history of malignancy. These patients' baseline demographic, treatment, rheumatological, and oncological data were collected. The neoplastic outcome (i.e., cancer recurrence or progression) after secukinumab start was then analyzed. Our study included 22 patients with spondyloarthritis. The most frequently reported oncological diagnosis was breast cancer (9 [41%] patients). Secukinumab was started after a median of 24 months following cancer diagnosis. At this time point, all but three patients were in oncological remission. No case of cancer relapse or progression was recorded over a median follow-up of 30 months. In the largest cohort reported to date to this regard, secukinumab was not associated with oncological recurrence or progression in patients with spondyloarthritis with a history of malignancy. Secukinumab may, therefore, represent a safe option in this clinical scenario.

Orbital/ocular inflammatory involvement in VEXAS syndrome: Data from the international AIDA network VEXAS registry.

VEXAS syndrome is a recently described monogenic autoinflammatory disease capable of manifesting itself with a wide array of organs and tissues involvement. Orbital/ocular inflammatory manifestations are frequently described in VEXAS patients. The objective of this study is to further describe orbital/ocular conditions in VEXAS syndrome while investigating potential associations with other disease manifestations. In the present study, twenty-seven out of 59 (45.8 %) VEXAS patients showed an inflammatory orbital/ocular involvement during their clinical history. The most frequent orbital/ocular affections were represented by periorbital edema in 8 (13.6 %) cases, episcleritis in 5 (8.5 %) patients, scleritis in 5 (8.5 %) cases, uveitis in 4 (6.8 %) cases, conjunctivitis in 4 (6.8 %) cases, blepharitis in 3 (5.1 %) cases, orbital myositis in 2 (3.4 %) cases. A diagnosis of systemic immune-mediated disease was observed in 15 (55.6 %) cases, with relapsing polychondritis diagnosed in 12 patients. A significant association was observed between relapsing polychondritis and orbital/ocular involvement in VEXAS syndrome (Relative Risk: 2.37, 95 % C.I. 1.03-5.46, p = 0.048). Six deaths were observed in the whole cohort of patients after a median disease duration of 1.2 (IQR=5.35) years, 5 (83.3 %) of which showed orbital/ocular inflammatory involvement. In conclusion, this study confirms that orbital/ocular inflammatory involvement is a common finding in VEXAS patients, especially when relapsing polychondritis is diagnosed. This makes ophthalmologists a key figure in the diagnostic process of VEXAS syndrome. The high frequency of deaths observed in this study seems to suggest that patients with orbital/ocular involvement may require increased attention and more careful follow-up.

Development of a diagnostic prediction model for giant cell arteritis by sequential application of Southend Giant Cell Arteritis Probability Score and ultrasonography: a prospective multicentre study.

BACKGROUND: Giant cell arteritis is a critically ischaemic disease with protean manifestations that require urgent diagnosis and treatment. European Alliance of Associations for Rheumatology (EULAR) recommendations advocate ultrasonography as the first investigation for suspected giant cell arteritis. We developed a prediction tool that sequentially combines clinical assessment, as determined by the Southend Giant Cell Arteritis Probability Score (SGCAPS), with results of quantitative ultrasonography. METHODS: This prospective, multicentre, inception cohort study included consecutive patients with suspected new onset giant cell arteritis referred to fast-track clinics (seven centres in Italy, the Netherlands, Spain, and UK). Final clinical diagnosis was established at 6 months. SGCAPS and quantitative ultrasonography of temporal and axillary arteries with three scores (ie, halo count, halo score, and OMERACT GCA Score [OGUS]) were performed at diagnosis. We developed prediction models for diagnosis of giant cell arteritis by multivariable logistic regression analysis with SGCAPS and each of the three ultrasonographic scores as predicting variables. We obtained intraclass correlation coefficient for inter-rater and intra-rater reliability in a separate patient-based reliability exercise with five patients and five observers. FINDINGS: Between Oct 1, 2019, and June 30, 2022, we recruited and followed up 229 patients (150 [66%] women and 79 [34%] men; mean age 71 years [SD 10]), of whom 84 were diagnosed with giant cell arteritis and 145 with giant cell arteritis mimics (controls) at 6 months. SGCAPS and all three ultrasonographic scores discriminated well between patients with and without giant cell arteritis. A reliability exercise showed that the inter-rater and intra-rater reliability was high for all three ultrasonographic scores. The prediction model combining SGCAPS with the halo count, which was termed HAS-GCA score, was the most accurate model, with an optimism-adjusted C statistic of 0·969 (95% CI 0·952 to 0·990). The HAS-GCA score could classify 169 (74%) of 229 patients into either the low or high probability groups, with misclassification observed in two (2%) of 105 patients in the low probability group and two (3%) of 64 of patients in the high probability group. A nomogram for easy application of the score in daily practice was created. INTERPRETATION: A prediction tool for giant cell arteritis (the HAS-GCA score), combining SGCAPS and the halo count, reliably confirms and excludes giant cell arteritis from giant cell arteritis mimics in fast-track clinics. These findings require confirmation in an independent, multicentre study. FUNDING: Royal College of Physicians of Ireland, FOREUM.

Case report: Cytopenias in VEXAS syndrome - a WHO 2022 based approach in a single-center cohort.

VEXAS syndrome is an acquired autoinflammatory disease characterized in most cases by cytopenias and macrocytic anemia. Dyshematopoiesis is a frequent finding in chronic inflammatory conditions and therefore, cytopenias are not easily classified in VEXAS patients. Here we report a series of 7 patients affected by VEXAS associated cytopenias, treated at our center. The use of NGS, together with morphological assays, integrated with the WHO 2022 criteria, allowed to identify three subsets of VEXAS associated cytopenias: ICUS (idiopathic cytopenia of uncertain significance), CCUS (clonal cytopenia of uncertain significance) at high risk of clonal evolution, and MDS. This approach could help to better understand the nature of VEXAS associated cytopenias and to guide the use of specific targeted treatments in order to achieve long lasting responses.

New blood biomarkers and imaging for disease stratification and monitoring of giant cell arteritis.

Relapses and late complications remain a concern in giant cell arteritis (GCA). Monitoring strategies are required to effectively tailor treatment and improve patients' outcomes. Current monitoring of GCA is based on clinical assessment and evaluation of traditional inflammatory markers such as C reactive protein and erythrocyte sedimentation rate; however, this approach has limited value in patients receiving interleukin (IL)-6 blocking agents. New blood biomarkers that are less dependent on the IL-6 axis such as IL-23, B cell activating factor, osteopontin and calprotectin have been explored, but none of them has yet accumulated sufficient evidence to qualify as a routine follow-up parameter. Imaging techniques, including ultrasound and 18F-fluorodeoxyglucose positron emission tomography/computed tomography, potentially offer additional insights; however, the choice of the imaging method as well as its interpretation must be investigated further. Future studies are required to investigate the outcome of patients with GCA whose treatment decisions are based on traditional plus novel (laboratory and imaging) biomarkers as compared with those undergoing conventional monitoring strategies.

Autoantibody-Mediated Depletion of IL-1RA in Still's Disease and Potential Impact of IL-1 Targeting Therapies.

BACKGROUND: Adult-onset Still's disease (AOSD) and systemic juvenile idiopathic arthritis (sJIA) resemble a continuum of a rare, polygenic IL-1ß-driven disease of unknown etiology. OBJECTIVE: In the present study we sought to investigate a potential role of recently described autoantibodies neutralizing the interleukin-1(IL-1)-receptor antagonist (IL-1-Ra) in the pathogenesis of Still's disease. METHODS: Serum or plasma samples from Still's disease patients (AOSD, n = 23; sJIA, n = 40) and autoimmune and/or inflammatory disease controls (n = 478) were analyzed for autoantibodies against progranulin (PGRN), IL-1Ra, IL-18 binding protein (IL-18BP), and IL-36Ra, as well as circulating IL-1Ra and IL-36Ra levels by ELISA. Biochemical analyses of plasma IL-1Ra were performed by native Western blots and isoelectric focusing. Functional activity of the autoantibodies was examined by an in vitro IL-1ß-signaling reporter assay. RESULTS: Anti-IL-1-Ra IgG were identified in 7 (27%) out of 29 Still's disease patients, including 4/23 with AOSD and 3/6 with sJIA and coincided with a hyperphosphorylated isoform of endogenous IL-1Ra. Anti-IL-36Ra antibodies were found in 2 AOSD patients. No anti-PGRN or anti-IL-18BP antibodies were detected. Selective testing for anti-IL-1Ra antibodies in an independent cohort (sJIA, n = 34) identified 5 of 34 (14.7%) as seropositive. Collectively, 8/12 antibody-positive Still's disease patients were either new-onset active disease or unresponsive to IL-1 blocking drugs. Autoantibody-seropositivity associated with decreased IL-1Ra plasma/serum levels. Seropositive plasma impaired in vitro IL-1Ra bioactivity, which could be reversed by anakinra or canakinumab treatment. CONCLUSION: Autoantibodies neutralizing IL-1Ra may represent a novel patho-mechanism in a subgroup of Still's disease patients, which is sensitive to high-dose IL-1 blocking therapy.

Prevalence and characteristics of subclinical giant cell arteritis in polymyalgia rheumatica.

OBJECTIVE: The main objective of this study was to analyse the prevalence and characteristics of subclinical GCA in patients with PMR. METHODS: This was a cross-sectional multicentre international study of consecutive patients with newly diagnosed PMR without symptoms or signs suggestive of GCA. All patients underwent US of the temporal superficial, common carotid, subclavian and axillary arteries. Patients with halo signs in at least one examined artery were considered to have subclinical GCA. The clinical, demographic and laboratory characteristics of the PMR group without subclinical vasculitis were compared with subclinical GCA, and the pattern of vessel involvement was compared with that of a classical single-centre GCA cohort. RESULTS: We included 346 PMR patients, 267 (77.2%) without subclinical GCA and 79 (22.8%) with subclinical GCA. The PMR patients with subclinical GCA were significantly older, had a longer duration of morning stiffness and more frequently reported hip pain than PMR without subclinical GCA. PMR with subclinical GCA showed a predominant extracranial large vessel pattern of vasculitic involvement compared with classical GCA, where the cranial phenotype predominated. The patients with PMR in the classical GCA group showed a pattern of vessel involvement similar to classical GCA without PMR but different from PMR with subclinical involvement. CONCLUSION: More than a fifth of the pure PMR patients had US findings consistent with subclinical GCA. This specific subset of patients showed a predilection for extracranial artery involvement. The optimal screening strategy to assess the presence of vasculitis in PMR remains to be determined.

Subclinical giant cell arteritis increases the risk of relapse in polymyalgia rheumatica.

OBJECTIVE: The aim of the present study was to determine the clinical significance of subclinical giant cell arteritis (GCA) in polymyalgia rheumatica (PMR) and ascertain its optimal treatment approach. METHODS: Patients with PMR who fulfilled the 2012 European Alliance of Associations for Rheumatology/American College of Rheumatology Provisional Classification Criteria for PMR, did not have GCA symptoms and were routinely followed up for 2 years and were stratified into two groups, according to their ultrasound results: isolated PMR and PMR with subclinical GCA. The outcomes (relapses, glucocorticoid use and disease-modifying antirheumatic drug treatments) between groups were compared. RESULTS: We included 150 patients with PMR (50 with subclinical GCA) with a median (IQR) follow-up of 22 (20-24) months. Overall, 47 patients (31.3 %) had a relapse, 31 (62%) in the subclinical GCA group and 16 (16%) in the isolated PMR group (p<0.001). Among patients with subclinical GCA, no differences were found in the mean (SD) prednisone starting dosage between relapsed and non-relapsed patients (32.4±15.6 vs 35.5±12.1 mg, respectively, p=0.722). Patients with subclinical GCA who relapsed had a faster prednisone dose tapering in the first 3 months compared with the non-relapsed patients, with a mean dose at the third month of 10.0±5.2 versus 15.2±7.9 mg daily (p<0.001). No differences were found between relapsing and non-relapsed patients with subclinical GCA regarding age, sex, C reactive protein and erythrocyte sedimentation rate. CONCLUSIONS: Patients with PMR and subclinical GCA had a significantly higher number of relapses during a 2-year follow-up than patients with isolated PMR. Lower starting doses and rapid glucocorticoid tapering in the first 3 months emerged as risk factors for relapse.

Diagnostic capabilities, clinical features, and longitudinal UBA1 clonal dynamics of a nationwide VEXAS cohort.

VEXAS is a prototypic hemato-inflammatory disease combining rheumatologic and hematologic disorders in a molecularly defined nosological entity. In this nationwide study, we aimed at screenshotting the current diagnostic capabilities and clinical-genomic features of VEXAS, and tracked UBA1 longitudinal clonal dynamics upon different therapeutics, including allogeneic hematopoietic cell transplant. We leveraged a collaboration between the Italian Society of Experimental Hematology and of Rheumatology and disseminated a national survey to collect clinical and molecular patient information. Overall, 13/29 centers performed UBA1 genomic testing locally, including Sanger sequencing (46%), next-generation sequencing (23%), droplet digital polymerase chain reaction (8%), or combination (23%). A total of 41 male patients were identified, majority (51%) with threonine substitutions at Met41 hotspot, followed by valine and leucine (27% and 8%). Median age at VEXAS diagnosis was 67 years. All patients displayed anemia (median hemoglobin 9.1 g/dL), with macrocytosis. Bone marrow vacuoles were observed in most cases (89%). The most common rheumatologic association was polychondritis (49%). A concomitant myelodysplastic neoplasm/syndrome (MDS) was diagnosed in 71% of patients (n = 28), chiefly exhibiting lower Revised International Prognostic Scoring System risk profiles. Karyotype was normal in all patients, except three MDS cases showing -Y, t(12;16)(q13;q24), and +8. The most frequently mutated gene was DNMT3A (n = 10), followed by TET2 (n = 3). At last follow-up, five patients died and two patients progressed to acute leukemia. Longitudinal UBA1 clonal dynamics demonstrated mutational clearance following transplant. We collected a nationwide interdisciplinary VEXAS patient cohort, characterized by heterogeneous rheumatologic manifestations and treatments used. MDS was diagnosed in 71% of cases. Patients exhibited various longitudinal UBA1 clonal dynamics.

Still's disease continuum from childhood to elderly: data from the international AIDA Network Still's disease registry.

OBJECTIVE: Still's disease is more frequently observed in the paediatric context, but a delayed onset is not exceptional both in the adulthood and in the elderly. However, whether paediatric-onset, adult-onset and elderly-onset Still's disease represent expressions of the same disease continuum or different clinical entities is still a matter of controversy. The aim of this study is to search for any differences in demographic, clinical features and response to treatment between pediatric-onset, adult-onset and elderly-onset Still's disease. METHODS: Subjects included in this study were drawn from the International AutoInflammatory Disease Alliance Network registry for patients with Still's disease. RESULTS: A total of 411 patients suffering from Still's disease were enrolled; the disease occurred in the childhood in 65 (15.8%) patients, in the adult 314 (76.4%) patients and in the elderly in 32 (7.8%) patients. No statistically significant differences at post-hoc analysis were observed in demographic features of the disease between pediatric-onset, adult-onset and elderly-onset Still's disease. The salmon-coloured skin rash (p=0.004), arthritis (p=0.009) and abdominal pain (p=0.007) resulted significantly more frequent among paediatric patients than in adult cases, while pleuritis (p=0.015) and arthralgia (p<0.0001) were significantly more frequent among elderly-onset patients compared with paediatric-onset subjects. Regarding laboratory data, thrombocytosis was significantly more frequent among paediatric patients onset compared with adult-onset subjects (p<0.0001), while thrombocytopenia was more frequent among elderly-onset patients although statistical significance was only bordered. No substantial differences were observed in the response to treatments. CONCLUSIONS: Despite some minor difference between groups, overall, demographic, clinical, laboratory and treatments aspects of Still's disease were similarly observed in patients at all ages. This supports that pediatric-onset, adult-onset and elderly-onset Still's disease is the same clinical condition arising in different ages.

Efficacy of canakinumab in patients with Still's disease across different lines of biologic therapy: real-life data from the International AIDA Network Registry for Still's Disease.

Introduction: The effectiveness of canakinumab may change according to the different times it is used after Still's disease onset. This study aimed to investigate whether canakinumab (CAN) shows differences in short- and long-term therapeutic outcomes, according to its use as different lines of biologic treatment. Methods: Patients included in this study were retrospectively enrolled from the AutoInflammatory Disease Alliance (AIDA) International Registry dedicated to Still's disease. Seventy-seven (51 females and 26 males) patients with Still's disease were included in the present study. In total, 39 (50.6%) patients underwent CAN as a first-line biologic agent, and the remaining 38 (49.4%) patients were treated with CAN as a second-line biologic agent or subsequent biologic agent. Results: No statistically significant differences were found between patients treated with CAN as a first-line biologic agent and those previously treated with other biologic agents in terms of the frequency of complete response (p =0.62), partial response (p =0.61), treatment failure (p >0.99), and frequency of patients discontinuing CAN due to lack or loss of efficacy (p =0.2). Of all the patients, 18 (23.4%) patients experienced disease relapse during canakinumab treatment, 9 patients were treated with canakinumab as a first-line biologic agent, and nine patients were treated with a second-line or subsequent biologic agent. No differences were found in the frequency of glucocorticoid use (p =0.34), daily glucocorticoid dosage (p =0.47), or concomitant methotrexate dosage (p =0.43) at the last assessment during CAN treatment. Conclusion: Canakinumab has proved to be effective in patients with Still's disease, regardless of its line of biologic treatment.

Epidemiology and geographic clustering of Erdheim-Chester disease in Italy and France.

This geoepidemiological study, performed in Italy and France, shows that Erdheim-Chester disease is increasingly diagnosed and cases cluster in specific geographic areas, namely southern Italy and central France. Disease frequency inversely correlates with the Human Development Index.

High-dose anakinra in addition to standard of care including corticosteroids in patients with severe COVID-19 treated with non-invasive ventilation.

Management of COVID-19 patients experiencing persisting respiratory failure despite corticosteroids remains challenging. Data on high-dose intravenous anakinra (HD-ANK) in this context are lacking. We aimed to investigate the impact of HD-ANK on mortality in COVID-19 patients progressing to non-invasive ventilation (NIV) while receiving corticosteroids. We retrospectively analyzed the impact of HD-ANK on 28-day mortality in individuals hospitalized with COVID-19 necessitating NIV after corticosteroid initiation. A total of 256 patients were identified: 146 received standard-of-care only (SOC), and 110 received HD-ANK+SOC. The groups were well-balanced at baseline. In-hospital mortality at 28 days did not differ between the two groups. HD-ANK is not beneficial in patients with severe COVID-19 deteriorating despite corticosteroids.

Subclinical giant cell arteritis in polymyalgia rheumatica: Concurrent conditions or a common spectrum of inflammatory diseases?

Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are common conditions in older adults. Their clinical connection has been recognized over time, with many patients experiencing both conditions separately, simultaneously or in temporal sequence to each other. Early GCA detection is essential to prevent vascular damage, but identifying subclinical GCA in PMR patients remains a challenge and routine screening is not standard practice. Subclinical GCA prevalence in newly diagnosed PMR patients ranges from 23 to 29%, depending on the screening method. Vessel wall imaging and temporal artery biopsy can detect subclinical GCA. Epidemiology and trigger factors show similarities between the two conditions, but PMR is more common than GCA. Genetic and pathogenesis studies reveal shared inflammatory mechanisms involving dendritic cells, pro-inflammatory macrophages, and an IL-6 signature. However, the inflammatory infiltrates differ, with extensive T cell infiltrates seen in GCA while PMR shows an incomplete profile of T cell and macrophage-derived cytokines. Glucocorticoid treatment is effective for both conditions, but the steroid requirements vary. PMR overall mortality might be similar to the general population, while GCA patients with aortic inflammatory aneurysms face increased mortality risk. The GCA-PMR association warrants further research. Considering their kinship, recently the term GCA-PMR Spectrum Disease (GPSD) has been proposed.

The administration of methotrexate in patients with Still's disease, "real-life" findings from AIDA Network Still Disease Registry.

OBJECTIVES: To describe clinical characteristics of patients with Still's disease treated with methotrexate (MTX) and to assess drug effectiveness evaluating change in disease activity, reduction of inflammatory markers, and glucocorticoid (GC)-sparing effect. METHODS: Patients with Still's disease treated with MTX were assessed among those included in AIDA Network Still Disease Registry. RESULTS: In this registry, 171 patients with Still's disease were treated with MTX (males 43.3%, age 37.1 ± 16.0 years). They were mainly characterised by joint features and fever without a prominent multiorgan involvement. MTX was administered with GCs in 68.4% of patients, with other conventional synthetic DMARDs in 6.4%, and with biologic DMARDs in 25.1%. A significant reduction of the modified systemic score was observed, and 38.6% patients were codified as being in clinical remission at the end of follow-up. The concomitant administration of a biologic DMARD resulted a predictor of the clinical remission. Furthermore, a reduction of inflammatory markers and ferritin levels was observed following the administration of MTX. Additionally, a marked reduction of the dosage of concomitant GCs was identified, while 36.7% discontinued such drugs. Male gender appeared as a predictor of GC discontinuation. MTX was discontinued in 12.3% of patients because of adverse effects, and in 12.3% for lack of efficacy. CONCLUSIONS: Clinical characteristics of patients with Still's disease treated with MTX were described, mainly joint features and fever without a prominent multiorgan involvement. The clinical usefulness of MTX was reported in reducing the disease activity, decreasing the inflammatory markers, and as GC-sparing agent.

Intravenous versus subcutaneous tocilizumab in Takayasu arteritis: multicentre retrospective study.

OBJECTIVES: In this large multicentre study, we compared the effectiveness and safety of tocilizumab intravenous versus subcutaneous (SC) in 109 Takayasu arteritis (TAK) patients. METHODS: We conducted a retrospective multicentre study in referral centres from France, Italy, Spain, Armenia, Israel, Japan, Tunisia and Russia regarding biological-targeted therapies in TAK, since January 2017 to September 2019. RESULTS: A total of 109 TAK patients received at least 3 months tocilizumab therapy and were included in this study. Among them, 91 and 18 patients received intravenous and SC tocilizumab, respectively. A complete response (NIH <2 with less than 7.5 mg/day of prednisone) at 6 months was evidenced in 69% of TAK patients, of whom 57 (70%) and 11 (69%) patients were on intravenous and SC tocilizumab, respectively (p=0.95). The factors associated with complete response to tocilizumab at 6 months in multivariate analysis, only age <30 years (OR 2.85, 95% CI 1.14 to 7.12; p=0.027) and time between TAK diagnosis and tocilizumab initiation (OR 1.18, 95% CI 1.02 to 1.36; p=0.034). During the median follow-up of 30.1 months (0.4; 105.8) and 10.8 (0.1; 46.4) (p<0.0001) in patients who received tocilizumab in intravenous and SC forms, respectively, the risk of relapse was significantly higher in TAK patients on SC tocilizumab (HR=2.55, 95% CI 1.08 to 6.02; p=0.033). The overall cumulative incidence of relapse at 12 months in TAK patients was at 13.7% (95% CI 7.6% to 21.5%), with 10.3% (95% CI 4.8% to 18.4%) for those on intravenous tocilizumab vs 30.9% (95% CI 10.5% to 54.2%) for patients receiving SC tocilizumab. Adverse events occurred in 14 (15%) patients on intravenous route and in 2 (11%) on SC tocilizumab. CONCLUSION: In this study, we confirm that tocilizumab is effective in TAK, with complete remission being achieving by 70% of disease-modifying antirheumatic drugs-refractory TAK patients at 6 months.