ABSTRACT
BackgroundGCA is a critically ischemic large vessel vasculitis, varying in extent, severity and outcomes, hence requires disease stratification using clinical, laboratory and imaging parameters, for targeted management. Although DMARDs are used, the effectiveness in real life, such adjuvants remain un-elucidated. We performed a prospective, multi centre cohort study of new GCA stratified into remitting, relapsing, refractory, ischemic disease.ObjectivesWe assessed prognostic factors and compared critical outcomes such as remission with glucocorticoid (GC) monotherapy versus GC plus DMARDs in the first 12 months.MethodsHAS GCA study (1) recruited consecutive patients with new onset GCA from 7 centres (UK, Italy, Spain, Netherlands). diagnosis was confirmed used a modified GiACTA criteria at 6 months follow up. All underwent ultrasound (bilateral common, parietal, frontal temporal arteries, and axillary arteries) using accepted standard cut-off values [2]. GCA patients had US at baseline,1,3,6,12 months and halo count (HC) and Halo score (Temporal TAHS, axillary AAHS, total THS) assessed [3]. The primary outcome- remission at 12 months (absence of signs/symptoms, CRP<5 mg/dl, prednisolone < 5 mg daily). Results are reported as descriptive statistics.Results229 participants included in the study (GCA- 84 (36.68 %) (Figure 1). Study recruited during Covid pandemic,73 completed,11 lost to follow-up (died -7, withdrawn-4). The deceased/withdrawn patients (compared to completers) were older (80 v74 yrs, p=0.018), preponderantly male (73% v 36%, p=0.043) with visual symptoms (91% v 49%, p=0.010) partial/total sight loss (55% v 21%, p=0.024), lower CRP (21 v 68, p=0.061) and ESR (42 v 62, p= 0.317).Of 73 completers 36 required early DMARDs (<12 weeks) for refractory/relapsing/ischemic/GC related AEs. This group had more LV involvement (50% v 11%, p=0.0003), Remission attained at 12 months 32/36 (89%) in DMARD group was comparable to the remitting GC monotherapy group 33/37 (89%) with comparable cumulative GC doses (Figure 1, Table 1).At 12-months follow up, median TAHS, AAHS and THS reduced from 13 to 3, 12 to 9 and 21.5 to 12, respectively.ConclusionOur study suggests, elderly males with visual symptoms, sight loss, lower CRP are a high-risk group with increased mortality within GCA. Difficult to treat disease is seen in half of all patients especially with LV involvement. This group responds well to early DMARD use achieving remission comparable to the remitting group at 12 months. Current therapies fail to achieve remission in 9.5 % of cases. HS and HC show significant improvement mirroring clinical outcomes during first 12 months of therapy.References[1]Sebastian A et al. BMC Rheum. 2020[2]Schafer VS et al. Rheumatology 2017[3]van der Geest KSM et al. ARD 2020Table 1.comparison between the DMARD-used group and only GC group in all the GCA completed the 12 months follow upPatients' characteristicsGCA with completed follow-up (n=73)GCA treated with DMARD=36GCA not treated with DMARD=37Age, median (range) years73.5 (60-89)76 (60-89)Sex, Females, n (%)23 (64)24 (65)US halo score (HS)/IMT median (range)Temporal artery HS11 (0-23)13 (1-22)Axillary artery HS12 (0-21)12 (0-18)Axillary artery IMT (mm)0.77 (0.33-2.6)0.82 (0.39-1.21)Total HS22.5 (2-41)21 (5-40)Clinical features, n (%)Temporal headache25(69)30 (81)Scalp tenderness17 (47)19 (51)Jaw & Tongue claudication22 (61)24 (65)Polymyalgic symptoms21 (58)13 (35)Constitutional symptoms21 (58)18 (49)Any visual disturbance15 (42)21 (57)Partial or complete vision loss8 (22)7 (19)History of PMR6 (17)3 (8)Exam findings, n (%)Temporal artery abnormality24 (67)30 (81)AION/ CRAO8 (22)6 (16)Ocular nerve palsy1 (3)3 (8)Lab markers at baseline, median (range)CRP mg/dL,72.2 (6.4-292)59 (6-206)ESR mm/hr67 (9-130)57 (2-120)GC treatment, median (range)GC starting dose, (baseline)45 (0-60)50 (0-60)GC dose at 12m,5 (0-25)2.5 (0-10)Cumulative GC dose at 12m4627.5 (2600-10260.5)4622.5 (944-10737.5)Remission with prednisolone dose ≤5 mg at 12m, n (%)32 (89)33 (89)Acknowledgements:NIL.Disclosure of InterestsBhaskar Dasgupta Consultant of: Roche, Chugai, Sanofi, Grant/research support from: Roche, Sanofi, AbbVie, and GlaxoSmithKline, Kornelis van der Geest Speakers bureau: Roche, Grant/research support from: AbbVie, Alessandro Tomelleri: None declared, Pierluigi Macchioni: None declared, Giulia Klinowski: None declared, Carlo Salvarani: None declared, Abdul Kayani: None declared, Mohammad Tariq: None declared, Diana Prieto-Peña: None declared, Edoardo Conticini: None declared, Muhammad Khurshid: None declared, Sue Inness: None declared, Jo Jackson: None declared, Alwin Sebastian: None declared.
ABSTRACT
Background. Rituximab (RTX) is a chimeric monoclonal antibody that binds the CD20 molecule on the surface of B cells and leads to B cell depletion. RTX is recommended by the European League Against Rheumatism (EULAR) as off-label in patients affected by idiopathic inflammatory myopathies (IIM). The real-world experience has shown that hypogammaglobulinemia occurring early after anti-CD20 treatment can be multifactorial (active disease, effect of other drugs) and usually transient, with a minimal increase in the risk of infections. The present study aimed to analyse the differences in the rate of RTX-associated hypogammaglobulinemia in a cohort of IIM patients in clinical practice, as well as the onset of major infections and its correlation with hypogammaglobulinemia. Methods. Patients followed at Rheumatology Unit of Siena University Hospital from January 2020 to September 2021 were retrospectively enrolled. Inclusion criteria were as follows: fulfilment of disease-specific classification criteria 2017 EULAR criteria and /or Peter and Bohan criteria for dermatomyositis (DM) and polymyositis (PM), positivity of anti-synthetase antibody and typical clinical features for anti-synthetase syndrome (ASS) and the measurement of serum Ig levels at the time of RTX administration (maximum 2 weeks before) (T0) and 6 (T1) to 12 (T2) months later, consistently with previous studies. Ig serum levels, measured by standard nephelometry (normal ranges: IgG 700-1600 mg/dL, IgM 40-240 mg/dL, IgA 70-400 mg/dL) were assessed as part of routine clinical care. Hypogammaglobulinemia was defined as moderate (serum IgG <600 mg/dL) and severe (IgG <400 mg/dL), as previously reported. Results. Seven patients (mean+/-SD, 57.3+/-19.7 years;7 female) were enrolled. Three of them had diagnosis of DM, three ASS and one PM. Two patients showed MDA5-positivity, two JO1-positivity, one TIF1-gamma-positivity, one PL7-positivity and the other one PM/Scl-positivity. All patients had at least two organs involved, and 4 out of 7 (57%) suffered from interstitial lung disease. Before starting RTX treatment, three and four patients underwent at least one and two synthetic immunosuppressants. All patients underwent low dosage of corticosteroids, and four patients underwent concomitant synthetic immunosuppressants (2 hydroxychloroquine and 2 MTX). IgG concentrations were statically lower at T2 compared to those at baseline (p=0.0391). None of them showed severe hypogammaglobulinemia. Similarly, IgM concentration significantly decreased at T2 compared to those at baseline (p=0.0078). Two patients showed major infections and two patients had paucisymptomatic COVID-19 (one of them had twice). Corticosteroids dosages were inversely correlated with IgG T2 concentrations (p=0.040, r=-0.919). Conclusion. Hypogammaglobulinemia following RTX is uncommon in IIM and is more likely in patients with high glucocorticoids, immunosuppressants and CYC exposure. IgG monitoring at least 6 months after RTX treatment may be useful in stratifying patients to identify those who require closer monitoring. These results shine a spotlight for increased awareness of the role of immunoglobulin measurement before maintenance doses of RTX.
ABSTRACT
Background: Vaccinations against SARS-CoV-2 represent a fundamental tool in controlling the pandemic. To date, data on the safety of anti-SARS-CoV-2 vaccines in patients with rare rheumatic diseases, such as systemic vasculitis, are limited. Objectives: In this study we aimed at evaluating the safety of anti-SARS-CoV-2 vaccines in a multicentric cohort of patients with systemic vasculitis. Methods: Patients with systemic vasculitis from two Rheumatology centres who had received anti-SARS-CoV-2 vaccine were retrospectively examined. The primary outcome was to evaluate, in this multi-centric cohort, the occurence of a disease fare after the administration of the vaccine, defned as development of clinical manifestations related to vasculitis with a concomitant increase in serum infammatory markers. As a secondary outcome we aimed at evaluating, in a monocentric cohort of patients with vasculitis, the occurrence of adverse events (AEs) following vaccine administration compared to healthy controls (HC). Results: We examined 111 patients with systemic vasculitis (n=69 female, n=42 male), with a mean age of 64.3 (± 13) years. Sixty had ANCA-associated vas-culitis (AAV), fourty-two had Giant-Cell Arterities (GCA), five had Periarteritis Nodosa, four had Takayasu's arteritis. One-hundred and five patients received a mRNA vaccine and six a viral vector one. A disease fare occurred in only 2 patients (1.8%) after the frst dose of a mRNA vaccine: both had AAV (microscopic poliangioitis) and developed a pulmunary disease fare (respiratory failure requiring hospitalization and treatment with high-dose glucocorticoids). Of note, one of these patients had multiple previous comorbidities, including a severe COPD. Multivaried analysis, adjusted for age and sex, performed in a single monocentric cohort of patients with systemic vasculitis [n=60 (39 AAV, 21 GCA), 37 female, 23 male, mean age 71 (± 12.5) years] demonstrated a statistically sig-nifcant higher frequency of AEs in vasculitis patients compared to HC (p=0.015) after the frst dose of vaccination. No signifcant differences in the frequency of AEs in vasculitis patients compared to HC after the second dose were detected. All the AEs were mild in both groups (malaise was the most frequently reported);no serious AEs were reported. Conclusion: Our data show a very low incidence of disease fares after the administration of anti-SARS-CoV-2 vaccines in patients with systemic vasculitis. Patients with systemic vasculitis seem more prone to develop mild AEs after the frst dose of the vaccine. Taken together, this data suggest a good risk profile for anti-SARS-CoV-2 vaccine in patients with systemic vasculitis.
ABSTRACT
Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination plays a crucial role as pivotal strategies to curb the coronavirus dis-ease-19 (COVID-19) pandemic. Despite the mass-scale vaccination, literature data about the incidence of disease fares in IIM patients are still not reported as well as the immunological condition. Objectives: The present study aimed to describe the clinical status of patients affected by IIM after vaccination against COVID19 in order to assess the number of relapses or immune-mediated reactions in a cohort of Italian patients with such disease. Methods: We included all patients affected by IIM and followed by Myositis Clinic, Rheumatology and Respiratory Diseases Units, Siena University Hospital, Bari University Hospital, Policlinico Umberto I, Sapienza University, Rome, and Policlinico Paolo Giaccone, Palermo. Inclusion criteria were a recent (<3 months) clinical and serological assessment before the survey and a defnite diagnosis of dermatomyosi-tis, polymyositis and anti-synthetase syndrome. All patients underwent a telephone survey in order to establish their clinical status and potential relapses after vaccination. Results: A total of 119 IIM patients (median, IQR 58 (47-66) years;32 males) were consecutively enrolled. Fifty had a diagnosis of DM, 39 had PM and 30 had ASS. The median months of disease duration was 79.62±83.98. According to number of organs involvement, forty-two had only one, 45 had two organs involvement, 20 had three, 11 had four and one had five. The majority of them received two doses of COVID-19 vaccine, except four patients who refused the vaccination: 94 (78.9%) Cominarty, 16 (13.4%) Moderna, 5 (0.04%) AZ. Seven (0.06%) patients had fare after vaccination, the majority of them were mild except one major with three organs involved and one life-threatening with systemic involvement. In order to understand or predict the effect of demographic and clinical features on the fare development after vaccination, a logistic regression analysis was performed. The goodness-of-ft statistics showed a Chi2 associated with the Log ratio (L.R.) of 0.045. From the probability associated with the Chi-square tests, the Type II analysis showed the variable that most influences the development of fare was the number of organs involved (p=0.047). Sixty-eight patients received the third dose of COVID-19 vaccination: 51 (75%) Cominarty and 17 (25%) Moderna. Only one (0.01%) patient (the same who had life-threatening fare with systemic involvement after two doses) had fare after third dose and eventually died. Conclusion: Vaccines against SARS-CoV2 have provided, both in registratory studies and in preliminary real-life evidence, an overall good efficacy and safety. Nevertheless, only scanty data are available for rheumatic patients in general and the ones affected by IIM in particular. To the best of our knowledge, ours represent the largest cohort of IIM patients in which immunogenicity of anti-SARS-CoV2 vaccine was assessed. In line with real-life data from other diseases, we found a non-statistically signifcant risk of relapse in our patients, which occurred seldom, usually mild and in patients with a more severe and aggressive course of disease.