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2.
Clinical Immunology ; Conference: 2023 Clinical Immunology Society Annual Meeting: Immune Deficiency and Dysregulation North American Conference. St. Louis United States. 250(Supplement) (no pagination), 2023.
Article in English | EMBASE | ID: covidwho-20234193

ABSTRACT

Background: Lymphoproliferation is the persistent proliferation of lymphoid cells and it's incidence in inborn errors of immunity varies from 0.7 to 18%. Material(s) and Method(s): This is a retrospective analysis of patients referred to the department of Immunology, B. J. Wadia Hospital for Children, Mumbai between March 2017 to December 2022. Inclusion criteria consisted of 3 months duration of significant lymphadenopathy and/or splenomegaly or history of lymphoma. The clinical characteristics, laboratory and molecular findings of the included patients were analyzed. Result(s): A total of 66 patients were included. There was a male preponderance with male:female ratio of 25:8. Median age of onset of lymphoproliferation was 4.75 years(Range 1 year to 60 years). Splenomegaly was seen in 75%. Infections included recurrent pneumonia (14/66), recurrent ear infections(5/66), COVID(4/66), one episode of pneumonia(6/66), herpes zoster(3/66), recurrent subcutaneous abscess (3/66), abdominal koch(3/66), chronic sinusitis(2/66), dermatophytosis(2/66), esophageal candidiasis(2/66), recurrent malaria(1/66), recurrent varicella(1/66), cryptococcal meningitis(1/66), gram negative sepsis(1/66), BCG adenitis(1/66), pseudomonas osteomyelitis(1/66), impetigo (1/66), pseudomonas urinary tract infection (1/66), chicken pox(1/66), herpes keratitis(1/66), dengue(1/66), Other manifestations included Evans plus phenotype(10/66), Evans phenotype(8/66), Autoimmune hemolytic anemia(5/66), bronchiectasis(5/66), Type 1 diabetes(3/66), hyper reactive airway disease(2/66), inflammatory bowel disease(4/66), autoimmune thrombocytopenia(2/66), stroke(3/66), hemophagocytic lymphohistiocytosis(2/66), hypertriglyceridemia(2/66), hypothyroidism(2/66), celiac disease(1/66), Type 2 diabetes(1/66), autoimmune encephalitis(1/66), autoimmune hepatitis(2/66), anti-parietal cell antibody(1/66), arthritis(1/66), autoimmune enteropathy(1/66), systemic lupus erythromatosus(1/66), primary biliary cirrhosis requiring liver transplant(1/66), nephrotic syndrome(1/66), lymphoedema(1/66), hypersplenism(1/66), recurrent oral ulcers(1/66), gout(1/66), dermatitis(1/66), ovarian teratoma(1/66), alopecia areata(1/66). Hodgkin's lymphoma(HL) was the most common malignancy(9/66), followed by non Hodgkin lymphoma(NHL)(6/66), transformation from NHL to HL(1/66), Burkitt to T-cell lymphoma(1/66), HL to DLBCL(1/66), HL to anaplastic T-cell lymphoma(1/66). EBV driven lymphoproliferation was seen in biopsy of21/66. Genetic testing showed mutations in LRBA(11/66), PIK3CD(5/66), CTLA4(3/66), TET2(2/66), IL2RA (1/66), IL12RB1(1/66), BACH2(1/66), PRKCD(1/66), TNFSFR13B(1/66), TNFAIP3(1/66), FAS(2/66), FASL(1/66), Caspase8(1/66), CARD11(1/66), RTEL1(1/66), AICD(1/66), PIK3R1(1/66), IKBKB(1/66). Treatment included IVIG, chemotherapy, rituximab, sirolimus, abatacept, HSCT. Conclusion(s): All children with persistent lymphoproliferation, with or without autoimmunity and/or infections should be worked up for an underlying monogenic disorder of immune dysregulation. Lymphomas presenting at abnormal site and/or age, relapse and EBV driven lymphomas require further evaluation. Presence of monogenic cause helps in providing targeted therapy.Copyright © 2023 Elsevier Inc.

3.
Journal of Clinical Rheumatology ; 29(4 Supplement 1):S4, 2023.
Article in English | EMBASE | ID: covidwho-2323776

ABSTRACT

Objectives: Patients with immune-mediated diseases achieve lower seroconversion rates to COVID19 vaccines compared to healthy controls. The aim of this study was to assess the SARS-CoV-2-specific humoral and T-cell responses after a two-dose regimen of SARS-CoV-2 vaccine in patients with rheumatoid arthritis (RA). Method(s): Observational study. Patients with RA, >=18 years of age, who were vaccinated according to the Argentine National Health Ministry's vaccination strategy were included. Anti-SARS-CoV-2 IgG antibodies, neutralizing activity and specific T-cell responses were assessed after the first and second doses. Result(s): A total of 120 RA patients were included. Mostly, homologous regimens were used, including Gam-COVID-Vac (27.5%), ChAdOx1 (24.2%), BBIBP-CorV (22.5%) and BNT162b2 (0.8%), while the most frequent combination of vaccines was Gam-COVID-Vac/mRNA-1273 (21.7%). After the second dose 81.7% presented anti-SARS-CoV-2 antibodies, 70.0% neutralizing activity and 65.3% specific T-cell response. The use of BBIBP-CorV, treatment with abatacept (ABA) and rituximab (RTX) were associated with undetectable antibodies and no neutralizing activity after two doses of vaccine. BBIBP-CorV was also associated with the absence of T-cell response. The total incidence of adverse events was 357.1 events/1000 doses: significantly lower with BBIBP-CorV (166.7 events/1000 doses, p alpha 0.02). Conclusion(s): In this cohort of patients with RA who received 2 doses of COVID-19 vaccine, according to the Argentine strategic vaccination planwhich included homologous and heterologous regimens, two of ten did not develop IgG anti-SARS-CoV-2, 70% presented neutralizing activity and 65% specific T-cell response. The use of BBIBP-CorV was associated with deficient humoral and cellular response, while treatment with ABA and RTXaffected the development of IgG anti-SARS-CoV-2 and neutralizing activity.

4.
Rheumatology (United Kingdom) ; 62(Supplement 2):ii51, 2023.
Article in English | EMBASE | ID: covidwho-2326056

ABSTRACT

Background/Aims Patients with immune-mediated rheumatic diseases (IMRD) are commonly treated with immunosuppressors and are prone to infections. Recently introduced mRNA SARS-Cov2 vaccines have demonstrated extraordinary efficacy across all ages. Immunosuppressed patients were excluded from phase III trials with SARS-We aim to fully characterize B and T cell immune responses elicited by mRNA SARS-Cov2 vaccines in patients with rheumatic diseases under immunotherapies, and to identify which drugs reduce vaccine's immunogenicity. Methods Humoral, CD4 and CD8 immune responses were investigated in 147 SARS-Cov2-naive patients with selected rheumatic diseases under immunosuppression after a two-dose regimen of SARS-Cov2 mRNA vaccine. Responses were compared with age, gender, and diseasematched IMRD patients not receiving immunosuppressors and with healthy controls Results IMRD patients showed decreased seroconversion rates (63% vs 100%, p=0.04) and cellular immune responses (59% vs 100%, p=0.007). Patients on methotrexate achieved seroconversion in 62% of cases and cellular responses in 80% of cases. Abatacept deeply affected humoral and cellular responses. Rituximab (31% responders) and belimumab (50% responders) showed severely impaired humoral responses but cellular responses were often preserved. Antibody titers were reduced with mycophenolate and azathioprine but preserved with leflunomide. Conclusion IMRD patients exhibit impaired SARS-CoV-2 vaccine-immunogenicity, variably reduced with immunosuppressors. Among commonly used therapies, abatacept and B-cell depleting therapies show the most deleterious effects, while anticytokines preserved immunogenicity. The effects of cumulative methotrexate and glucocorticoid doses on immunogenicity should be considered. Humoral and cellular responses are weakly correlated, but CD4 and CD8 tightly correlate. Seroconversion alone might not reflect the vaccine's immunogenicity.

6.
Vaccine ; 41(20): 3247-3257, 2023 05 11.
Article in English | MEDLINE | ID: covidwho-2295191

ABSTRACT

OBJECTIVES: To elucidate antibody responses after the second and third dose of COVID-19 vaccine in patients with inflammatory rheumatic diseases (IRD) treated with biologic/targeted disease modifying anti-rheumatic drugs (b/ts DMARDs). METHODS: Antibody levels to antigens representing spike full length protein and spike S1 were measured before vaccination, 2-12 weeks after the second dose, before and after the third dose using multiplex bead-based serology assay. Positive antibody response was defined as antibody levels over cut off (seropositivity) in seronegative individuals or ≥ 4-fold increase in antibodies in individuals seropositive for both spike proteins. RESULTS: Patients (n = 414) receiving b/ts DMARDs (283 had arthritis, 75 systemic vasculitis and 56 other autoimmune diseases) and controls (n = 61) from five Swedish regions participated. Treatments groups were: rituximab (n = 145); abatacept (n = 22); Interleukin 6 receptor inhibitors [IL6i (n = 79)]; JAnus Kinase Inhibitors [JAKi (n = 58)], Tumour Necrosis Factor inhibitor [TNFi (n = 68)] and Interleukin12/23/17 inhibitors [IL12/23/17i (n = 42)]. Percentage of patients with positive antibody response after two doses was significantly lower in rituximab (33,8%) and abatacept (40,9%) (p < 0,001) but not in IL12/23/17i, TNFi or JAKi groups compared to controls (80,3%). Higher age, rituximab treatment and shorter time between last rituximab course and vaccination predicted impaired antibody response. Antibody levels collected 21-40 weeks after second dose decreased significantly (IL6i: p = 0,02; other groups: p < 0,001) compared to levels at 2-12 week but most participants remained seropositive. Proportion of patients with positive antibody response increased after third dose but was still significantly lower in rituximab (p < 0,001). CONCLUSIONS: Older individuals and patients on maintenance rituximab have an impaired response after two doses of COVID-19 vaccine which improves if the time between last rituximab course and vaccination extends and also after an additional vaccine dose. Rituximab patients should be prioritized for booster vaccine doses. TNFi, JAKi and IL12/23/17i does not diminished humoral response to primary and an additional vaccination.


Subject(s)
Antirheumatic Agents , COVID-19 , Rheumatic Diseases , Humans , COVID-19 Vaccines , COVID-19/prevention & control , Abatacept , Rituximab/therapeutic use , Sweden , Antirheumatic Agents/therapeutic use , Rheumatic Diseases/drug therapy , Interleukin-12 , Antibodies, Viral
7.
Cardiooncology ; 9(1): 15, 2023 Mar 20.
Article in English | MEDLINE | ID: covidwho-2272504

ABSTRACT

BACKGROUND: Immune checkpoint inhibitors (ICIs) are currently widely used for treatment of various types of cancers. ICI-induced myocarditis, though uncommon, accounts for high risk of major adverse cardiac events and mortality, which makes appropriate diagnosis important. We here present a unique, challenging case of ICI-induced, refractory and isolated right ventricular (RV) myocarditis. CASE PRESENTATION: A 32-year-old female with breast cancer presented with newly onset chest pain and dyspnea shortly after initiation of Pembrolizumab. Coronary angiography showed normal coronary arteries and a cardiac magnetic resonance (CMR) revealed myocarditis involving the right ventricle with chamber dilation and severe dysfunction. ICI therapy was stopped, and high dose steroid therapy was initiated and symptoms resolved. However, three months after initial presentation, the patient was hospitalized for DKA and decompensated right heart failure, and a repeat cardiac MRI at that time showed recurrent, isolated right ventricular myocardial inflammation/edema without LV involvement. High dose steroid therapy was started again and at 6-month follow up, surveillance CMR continued to show persistent right-sided myocarditis, patient was eventually treated with Abatacept with resolution of HF symptoms, RV dysfunction and biomarkers at 10-month follow up. CONCLUSIONS: We describe a unique case of isolated ICI-induced right ventricular myocarditis leading to right ventricular failure, that was refractory despite ICI therapy cessation and immune suppression by repeated high dose steroids. Co-stimulatory pathway modulation with Abatacept eventually lead to the normalization of RV function and dilation ten months after initial myocarditis onset.

8.
International Journal of Rheumatic Diseases ; 26(Supplement 1):2023/11/10 00:00:00.000, 2023.
Article in English | EMBASE | ID: covidwho-2230725

ABSTRACT

Patients with immune mediated rheumatic and musculoskeletal diseases (RMD), including lupus, may develop more severe COVID 19 infection than the general population. Several medicines used in treatment of systemic lupus erythematosus (SLE), such as glucocorticoid, increases the risk of Covid 19 infection, especially at dose higher than 10 mg. The use of immunosuppression may have a role in altering the immune response to infection, therefore the experts recommend to use the good but safe alternatives, if available. However in manage acute or critical condition, established therapies may be more beneficial then alternatives to control the disease activity. Evidence for discontinuing immunosuppressants in RMD patients with COVID-19 is low, but the experts strongly recommended discontinuing them and weakly recommended to re-introduce them at least 2 weeks after recovery from acute COVID-19, but this may need to be individualized based on the clinical scenario and the judgment of physician. Lupus patients are recommended to receive SARS-CoV- 2 vaccine, as long as they do not have an allergy to vaccine components. Several studies revealed that there was no significant change in lupus disease activity after vaccination, however a study using BNT162b2 COVID-19 vaccine reported mild local reactogenicity in SLE and RA patients, such as redness and swelling. More frequent systemic reactogenicity, such as fever, fatigue, headache, chills, muscle and join pain, and vomiting, however, not more severe compared to healthy controls. This study adds to the notion that the vaccine is safe and well tolerated in patients with SLE and RA. Neutralizing antibody levels after COVID-19 vaccination were significantly lower than control population. The risk factors for reduced immunogenicity included older age and treatment with glucocorticoids, mycophenolate, rituximab and abatacept, and type of vaccines. Adjusting the immunosuppression dosage schedule was suggested and considered an individual condition. A COVID-19 vaccine booster is encouraged for patients with autoimmune inflammatory rheumatic disease, including lupus. If they have completed the primary COVID vaccine series of 3 doses and are expected to have mounted an inadequate vaccine response, they should receive supplemental doses (e.g., >=2 additional boosters, for a total of five doses) as recommended by the CDC for immunocompromised individuals.

9.
Expert Opin Pharmacother ; 23(17): 1887-1891, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2082122

ABSTRACT

INTRODUCTION: The pathogenesis of severe COVID-19 is due, in part, to dysregulation of the human immune system in response to SARS-CoV-2 infection. Immune cells infected with SARS-CoV-2 can trigger a hyperinflammatory response of both the adaptive and innate immune system that has been associated with severe disease, hospitalization, and death, and better treatment options are urgently needed. AREAS COVERED: A mainstay of therapy for COVID-19 involves an antiviral agent, remdesivir, in combination with a systemic corticosteroid, dexamethasone. EXPERT OPINION: The addition of a second immunomodulator, such as an interleukin-6 inhibitor or a Janus kinase inhibitor, has been associated with clinical benefit in a subset of patients with moderate-to-severe disease, but their use remains controversial. This manuscript reviews what is known about the approach to treatment of severe COVID-19 and examines how immunomodulators such as infliximab and abatacept may alter clinical management and COVID-19 research in the years ahead based on the results of randomized, controlled trials.


Subject(s)
COVID-19 Drug Treatment , Humans , SARS-CoV-2 , Antiviral Agents/therapeutic use , Hospitalization
10.
Swiss Medical Weekly ; 152(Supplement 261):2S, 2022.
Article in English | EMBASE | ID: covidwho-2058360

ABSTRACT

Patients with inflammatory rheumatic diseases (IRD) have an increased risk for a worse COVID-19 outcome, and impaired immune responses following mRNA COVID-19 vaccines have been observed. In this prospective observational study, we compared the anti-S1 response following vaccination with BNT162b2 and mRNA- 1273 in a large cohort of IRD patients and assessed the effect of different immunomodulatory treatments. Patients from SCQM, the Swiss IRD cohort, who assented to an mRNA COVID-19 vaccine were recruited into the study between 3/2021-9/2021. Participants answered the study questionnaire via the mySCQM patient app and provided self-collected capillary blood samples at baseline, 4, 12, and 24 weeks post second vaccine dose. Samples were tested for IgG antibodies against the S1 domain of the SARS-CoV-2 spike protein using the EUROIMMUN ELISA. We examined differences in antibody titres depending on the vaccine and treatment received, while adjusting for age and history of SARSCoV- 2 infection, by applying mixed effects continuous outcome logistic regression models at each timepoint. Eligible samples were obtained from 564 IRD patients (mean age 53 y (s.d. 12 y), 66% female) with 36% RA, 37%, axSpA, 21% PsA, and 6% UA (undifferentiated arthritis), on no medication (no DMARD & no steroids 15%), csDMARD (9%), TNFi (48%), IL-6/17/23i (14%), JAKi (6%), rituximab (4%), abatacept (3%), and PDE4i (1%) in mono/combination therapy at baseline. 10% of patients had a past SARS-CoV-2 infection, 54% received BNT162b2, 46% mRNA-1273. Independently of the disease, treatment, and history of SARS-CoV- 2 infection, the odds of having higher anti-S1 titres at 4, 12, and 24 weeks post second vaccine dose were, respectively, 3.3, 3.9, and 3.8 times higher with mRNA-1273 compared to BNT162b2 for the average-aged patient of this population (p <0.0001). Moreover, with every year of age, the odds of higher anti-S1 levels increased by 3% to 5% following mRNA-1273 vs BNT162b2 vaccination (p <0.05), indicating an additional benefit for elderly IRD patients. Among monotherapies, rituximab, abatacept, JAKi, and TNFi had the highest odds of reduced anti-S1 responses compared to no medication. Patients on specific combination therapies showed significantly reduced antibody responses compared to respective monotherapies. Our results suggest that in IRD patients, vaccination with mRNA- 1273 vs BNT162b2 results in higher anti-S1 antibody titres, and has an additional benefit in elderly patients.

11.
Medical Letter on Drugs and Therapeutics ; 63(1637):177-184, 2021.
Article in English | EMBASE | ID: covidwho-2057493
12.
Genes (Basel) ; 13(8)2022 07 24.
Article in English | MEDLINE | ID: covidwho-2023336

ABSTRACT

Multiple sclerosis (MS) is an autoimmune neurodegenerative disorder of the central nervous system that presents heterogeneous clinical manifestations and course. It has been shown that different immune checkpoints, including Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4), can be involved in the pathogenesis of MS. CTLA-4 is a critical regulator of T-cell homeostasis and self-tolerance and represents a key inhibitor of autoimmunity. In this scopingreview, we resume the current preclinical and clinical studies investigating the role of CTLA-4 in MS with different approaches. While some of these studies assessed the expression levels of CTLA-4 on T cells by comparing MS patients with healthy controls, others focused on the evaluation of the effects of common MS therapies on CTLA-4 modulation or on the study of the CTLA-4 blockade or deficiency in experimental autoimmune encephalomyelitis models. Moreover, other studies in this field aimed to discover if the CTLA-4 gene might be involved in the predisposition to MS, whereas others evaluated the effects of treatment with CTLA4-Ig in MS. Although these results are of great interest, they are often conflicting. Therefore, further studies are needed to reveal the exact mechanisms underlying the action of a crucial immune checkpoint such as CTLA-4 in MS to identify novel immunotherapeutic strategies for MS patients.


Subject(s)
CTLA-4 Antigen , Encephalomyelitis, Autoimmune, Experimental , Multiple Sclerosis , Animals , Autoimmunity/genetics , CTLA-4 Antigen/genetics , Encephalomyelitis, Autoimmune, Experimental/genetics , Encephalomyelitis, Autoimmune, Experimental/pathology , Humans , Multiple Sclerosis/drug therapy , Multiple Sclerosis/genetics , T-Lymphocytes
13.
Ther Adv Musculoskelet Dis ; 14: 1759720X221116408, 2022.
Article in English | MEDLINE | ID: covidwho-2009255

ABSTRACT

Background: The results of randomized controlled (RCT) and retrospective studies have expanded the armamentarium of drugs for systemic sclerosis (SSc) - interstitial lung disease (ILD) treatment. The correct positioning of these drugs is not yet clarified. Objectives: Systemic literature review (SLR) on rituximab (RTX), tocilizumab (TCZ), nintedanib and abatacept (ABT) for the treatment of SSc-ILD. The results of the SLR were used to create a dedicated survey. Design: The study was performed as a systematic review. Data sources and methods: the SLR was performed using the following terms: "(systemic sclerosis OR scleroderma) AND (interstitial lung disease OR lung fibrosis OR pulmonary fibrosis) AND (rituximab OR tocilizumab OR abatacept OR nintedanib)". The results of the SLR were integrated in a survey including 8 domains. These were sent to all EUSTAR members and to the participants of the 2020 Scleroderma World Congress. Results: 41 studies (34 on RTX, 5 on TCZ, 2 on ABT, and 1 on nintedanib) were identified. RCTs supported the use of TCZ and nintedanib, while retrospective studies supported the use of RTX for SSc-ILD. No clear data were obtained about ABT. The survey showed that RTX is the most available option (96%) whereas the most frequent reason for targeted therapy introduction is lung progression while on csDMARDs (86% RTX, 59% TCZ and 63% nintedanib). Combination therapy was the most frequently mentioned therapeutic scheme for nintedanib (75%) and RTX (63%). Physicians' perception of safety was similar for all drugs, while drug efficacy was the same for RTX and nintedanib, followed by TCZ (4.8 ± 2). The most frequently raised concerns pertained to efficacy, safety and combination regimens. Conclusion: Our SLR supports the use of RTX, TCZ and nintedanib for SSc-ILD patients and underlines the need for more data about upfront combination versus monotherapy. It also highlighted the need to identify predictors supporting drug choice according to both pulmonary and extra-pulmonary manifestations.

14.
Annals of the Rheumatic Diseases ; 81:1028, 2022.
Article in English | EMBASE | ID: covidwho-2009194

ABSTRACT

Background: Vacuoles, E1 enzyme, X-linked, autoinfammatory, somatic (VEXAS) syndrome is a recently identifed disorder caused by somatic mutations in the UBA1 gene of myeloid cells. Various manifestations of pulmonary involvement have been reported, but a detailed description of lung involvement and radiologic fndings is lacking. Objectives: To describe lung involvement in VEXAS syndrome. Methods: A retrospective cohort study was conducted of all patients iden-tifed at the Mayo Clinic with VEXAS syndrome since October 2020. Clinical records and chest high resolution computed tomography (HRCT) scans were reviewed. Results: Our cohort comprised 22 white men with a median age of 69 years (IQR 62-74, range 57-84). Hematologic disorders including multiple myeloma, myelodysplastic syndrome and pancytopenia were present in 10 patients (45%), rheumatologic diseases including granulomatosis with poly-angiitis, IgG4-related disease, polyarteritis nodosa, relapsing polychondritis, and rheumatoid arthritis were found in 10 patients (45%), and 4 patients had dermatologic presentations including Sweet syndrome, Schnitzer-like syndrome or drug rash with eosinophilia skin syndrome (DRESS). VEXAS syndrome-related features included fever (18, 82%), skin lesions (20, 91%), lung infiltrates (12, 55%), chondritis (10, 45%), venous thromboembolism (12, 55%), macrocytic anemia (21, 96%), and bone marrow vacuoles (21, 96%). Other manifestations observed were arthritis, scleritis, hoarseness and hearing loss. Median erythrocyte sedimentation rate (ESR) was 69 mm/1st hour (IQR 34.3-118.8) and median C-reactive protein (CRP) of 55.5 mg/dL (IQR 11.4-98.8). The somatic mutations affecting methionine-41 (p.Met41) in UBA1 gene were: 11 (50%) p.Met41Thr, 7 (32%) p.Met41Val, 2 (9%) p.Met41Leu, and 2 (9%) in the splice site. All patients received glu-cocorticoids (GC) (median duration of treatment was 2.6 years);21 (96%) received conventional immunosuppressive agents (methotrexate, aza-thioprine, mycophenolate, leflunomide, cyclosporin, hydroxychloroquine, tofacitinib, ruxolitinib) and 9 (41%) received biologic agents (rituximab, tocilizumab, infliximab, etanercept, adalimumab, golimumab, abatacept). Respiratory symptoms included dyspnea and cough present in 21 (95%) and 12 (55%), respectively, and were documented prior to VEXAS diagnosis. Most of the patients were non-smokers (14, 64%) and obstructive sleep apnea (OSA) was present in 11 patients (50%). Seven patients (32%) used non-invasive ventilation, 6 used C-PAP, and 1 used Bi-PAP. Bronchoalveolar lavage (BAL) was available in 4 patients, and the findings were compatible with neutrophilic alveolitis in 3. Two patients had lung biopsies (2 transbronchial and 1 surgical) that showed ATTR amyloidosis and organizing pneumonia with lymphoid interstitial pneumonia, respectively. Pulmonary function tests were available in 9 (41%) patients and showed normal results in 5;3 patients had isolated reduction in DLCO and 1 with mild restriction. On chest HRCT, 16 patients (73%) had parenchymal changes including ground-glass opacities in 9, septal thickening in 4, and nodules in 3;pleural effusions were present in 3 patients, air-trapping in 3 patients and tracheomalacia in 1 patient. Follow-up chest HRCT was available for 8 patients (36%), the ground-glass opacities resolved in 5 patients, 3 patients manifested new or increased ground-glass opacities, and 1 patient had increased interlobular septal thickening. After 1 year of follow-up, 4 patients (17%) had died;3 due to pneumonia (2 COVID-19,1 bacterial) and 1 due to heart failure. VEXAS flares occurred in 18 patients (82%), the maximum number of relapses was 7, and they were mainly managed with GC and with changes in the immuno-suppressive regimen. Conclusion: Pulmonary involvement was documented by chest HRCT in most patients with VEXAS syndrome. Respiratory symptoms occurred in over one half of patients and about 20% had PFT abnormalities. The pulmonary manifestations of VEXAS are nonspecifc and characterized predominantly by infamma-tory parenchymal involvement.

15.
Annals of the Rheumatic Diseases ; 81:973, 2022.
Article in English | EMBASE | ID: covidwho-2009156

ABSTRACT

Background: Coronavirus vaccines have been widely applied all over the world after the coronavirus pandemic. There are inactivated vaccines and mRNA vaccines in our country. There is no clear guideline for the vaccination programs of patients receiving immunosuppressive therapy, especially childhood. Objectives: For this reason, we wanted to evaluate the frequency of side effects developed after covid-19 vaccine in pediatric patients diagnosed with rheumatic disease using biological therapy and nonbiologic disease modifying drugs Methods: A total of 226 patients over the age of 12, who were followed up in the pediatric rheumatology clinic of the University of Health Sciences, Umraniye Training and Research Hospital, using biological therapy and were vaccinated against Covid-19, were included in the study. The standard questionnaire forms were flled in face-to-face after each administration for both vaccines. The patient, who had any serious side effects, was followed up in the hospital. Results: Of the 226 patients included in the study, 97 were male and 128 were female. Their mean age was 16.4 + 2.4. It was determined that 88.4% (n=200) of the patients had mRNA vaccine and 11.6% (n=26) had inactivated vaccine. 105 of the patients were using biologic drugs during vaccination. Of these, 63 (27.9%) patients were treated with anti-TNF drugs (46 adalimumab, 10 etanercept, 6 infix-mab), 32 patients were anti-il-1 (30 canakinumab, 2 anakirna), 4 patients were anti-il-6, 3 patients were anti-il-17, 3 patient was receiving abatacept and 1 patient was receiving rituximab. 121 patients were using DMARDs. Of these, 61 were using colchicine. 26.5% (n=60) of the patients had covid infection before vaccination. Side effects were observed in 180 of our patients. No side effects were observed in 46 patients. Pain at the injection site was the most common among them, 72.6% (n=164). Headache was seen in 16.8% (n=38) of the patients, myalgia in 18.1% (n=41), fever in 16.4% (n=37) and arthralgia in 6.6% (n=15). The frequency of serious adverse events was determined as 0.9%(n=2). Both patients were followed up in the ward. When the patients were compared in terms of covid infection and gender, there was no signifcant difference in the frequency of side effects. When the vaccines were compared, the incidence of side effects in the mRNA vaccine was statistically signifcantly higher (p=0.001). Pain at the injection site was signifcantly less frequent in the inactivated vaccine (p=0.004). In terms of drug distribution, there was no signifcant difference in the frequency of side effects between patients using biologic drugs and DMARDs. p=0.004) There was no statistically signifcant difference in the frequency of side effects when the patients using dmard were compared as colcicine and other dmards. Conclusion: In our study, we have shown that the use of vaccines in individuals with adolescent rheumatological diseases is safe and that the biological treatments used by the patients do not cause an increase in the risk of vaccine side effects. In addition;We have shown in our study that the side-effect profile of the inactivated vaccine used in our country is milder than the mRNA vaccine, and that it affects daily life less. Another result of our study was that anti-TNF drugs could cause a decrease in pain sensation due to the relationship of anti-TNF with pain pathways.

16.
Annals of the Rheumatic Diseases ; 81:969, 2022.
Article in English | EMBASE | ID: covidwho-2009117

ABSTRACT

Background: Although it prevents severe forms of the disease, vaccination does not completely protect against the occurrence of COVID19 disease. If, DMARDs used have been associated with variable humoral response to SARS-CoV-2 vaccination, the impact of their use after SARS-CoV-2 natural infection have been poorly studied. Objectives: To characterize humoral response after SARS-CoV-2 infection and viral persistence in the nasopharyngeal sphere (NP), stools and blood of patients with rheumatic disease under DMARDs, and compared to healthy controls. Methods: Prospective monocentric longitudinal study including patients with rheumatoid arthritis or spondyloarthritis under DMARDs and with a confrmed SARS-CoV-2 infection (positive NP PCR and/or positive serology and/or pathognomonic thoracic tomography (CT)) during the frst or second wave of the COVID pandemic. Patients were followed up until one year after infection and humoral response was assessed before vaccination. Serum IgG and IgA antibodies against spike (S) and nucleocapsid (N) proteins were measured at every visit. Viral persistence was assessed at the early visit in the NP and stools using conventional RT-PCR and in the blood using a high sensitive technique (droplet digital PCR). Results: Between June 2020 and July 2021, we include 96 patients (50 SpA and 46 RA) with a mean age of 53 +/-14 years and 20 healthy controls (mean age 49 ± 16 years) corresponding to relatives of patients (spouses, children) living together and infected at the same time. The immune responses were analyzed according to 6 treatment groups: methotrexate (MTX)/salazopyrine (SLZ) monotherapy (n=17/2);anti-TNF monotherapy (n=24), anti-TNF + MTX (n=23);rituximab (RTX) (n=11);anti-IL17 or-23 (n=8);others (n=11). Visits were made at 1 month (29 ±13 days;n=18), 3 months (110 ±23 days;n=67), 6 months (231 ±35 days;n=48) and 12 months (368 ± 19 days;n=19) after infection. The anti-S and anti-N IgG Ab titers were not signifcantly different in the 6 treatment groups and the control population at 3 months. A signifcant decrease in anti-S IgA Ab titers was noted in the group treated with RTX (p=0.007) and with molecules targeting the IL17/23 pathway (p=0.007). A similar but non-signifcant trend was observed in these same treatment groups for anti-N IgA Ab (p=0.07). The titers of anti-SARS-CoV-2 antibodies at M3, was not associated with a severe COVID disease. Detection of SARS-Cov-2 RNA in stools and serum was negative for all samples taken at 1 month or 3 months. 4 patients (2 RA treated with abatacept/RTX and 2 SpA treated with anti-TNF/secukinumab) had a positive RT-PCR NP with low to very low viral load at the 1-month visit (mean Ct 36). None of these 4 patients had had a severe form of COVID19 infection. Conclusion: DMARDs-treated patients with previous proven COVID-19 did not seem to alter IgG Ab response but RTX and anti-IL17/-IL-23 might alter IgA humoral response. This lower immune response was not associated with a more severe disease. In these patients, new infection may not be considered as a full boost for the immune system. DMARDs did not induce viral persistence in the serum, the NP or in the stool.

17.
Annals of the Rheumatic Diseases ; 81:1691-1692, 2022.
Article in English | EMBASE | ID: covidwho-2009082

ABSTRACT

Background: In the current situation of the SARS-CoV-2 pandemic, the Spanish Society of Rheumatology recommends vaccination of patients with chronic infammatory diseases (CID) under treatment with biological DMARDs (bDMARDs). However, the data regarding the generation of protective antibody titers after mRNA vaccines in patients with CID is limited. Objectives: To determine the seroconversion rate and safety after the SARS-CoV-2 vaccine in patients with CID under treatment with bDMARDs Methods: Cross-sectional observational study of 81 patients with CID from the HURS in Córdoba, who have received full vaccination for SARS-CoV-2 (without having previously suffered from COVID-19 disease) according to national guidelines. A determination of specifc IgG-type antibodies against the trimeric spike protein of SARS-CoV2 was performed on all of them. The chemilumines-cence technique with the kit was used in serum samples taken 4-5 weeks after administration of the second dose of the vaccine. Information about sociode-mographic characteristics, disease, type of bDMARDs, concomitant treatments and adverse effects after the second dose of the vaccine were collected in each patient. Results: 81 patients were included (mean age 59.5, 72.8% females). 50.6% of patients had RA, 17.3% SpA, 11% PsoA and 18.5% other CID. 23.5% were under treatment with Rituximab, 38.8% antiTNF, 13.6% Tocilizumab, 9.9% abatacept, 5% anti-JAK and 14.2% under other treatments. Anti-SARS-CoV-2 antibodies and neutralizing activity were detected in 80% of study participants. Rituximab treatment was signifcantly associated with negative seroconver-sion in comparison with patients under antiTNF treatment (OR 84.0 (95%CI 12.9-1709.2)). No interaction was found between the bDMARDs treatment and the type of vaccine with regard to the seroconversion, nor between bDMARDs and concomitant synthetic DMARD. When we evaluated IgG titers against the spike protein of SARS-CoV2, we found that patients under treatment with Rituximab showed the lowest titers levels in comparison with patients with other treatments (Figure 1, Table 1). In addition, patients who received AstraZeneca vaccine developed lower titers of antibodies in comparison with patients who received Pfzer (Table 1). Interestingly, among patients with antiTNF treatment, AstraZeneca was associated with lower IgG titers in comparison with Pfzer and Moderna [405.9 (553.0) vs. 1084.1 (791.2) vs. 1264.0 (1012.6), p=0.016, respectively]. No differences between vaccines were found in patients with the other type of bDMARDs. Only 18.9% presented mild adverse effects. No serious adverse effects were observed and no patient experienced a disease fare after vaccination. Conclusion: Our results show that SARS-CoV-2 mRNA vaccines produce sero-conversion in most patients with CID, except in the case of patients with rituxi-mab. No severe adverse effects or CID reactivation were found. Despite the small number of patients included, this study suggests the need for revaccination in the group of patients treated with rituximab or vaccinated with Astrazeneca.

18.
Annals of the Rheumatic Diseases ; 81:1687, 2022.
Article in English | EMBASE | ID: covidwho-2009051

ABSTRACT

Background: Coronavirus SARS-CoV-2 and its associated disease COVID-19 have become a worldwide pandemic since its frst case in 12/2019. Since approvement of the frst vaccines against COVID-19 in Europe in 12/2020 a large vaccination campaign was started. Our patients with infammatory diseases (ID) were graded as higher risk, thus an early vaccination was possible. Many of our patients used the possibility and got vaccinated. Until now, there is few knowledge about the efficacy and safety of vaccination in patients with rheumatic disorders. There are some reports of less vaccination response in patients with ID (1). First reports of those patients with rheumatological disorder and infection with SARS-CoV2 are available (1,2). Nevertheless, there is few knowledge about SARS-CoV2-infection in patients with ID after vaccination against COVID-19, yet. Objectives: The aim of our study was to evaluate, how many patients got infected with SARS-CoV2 after vaccination against COVID-19 and the course of the disease. Methods: All consecutive patients of the routine follow up visits from 07/2021 to 01/2022 in our rheumatological outpatient center were questioned for SARS-CoV2-infection. In case of infection, they were questioned for vaccination status and the course of the disease. Results: N=1206 patients could be evaluated. N=1183/1206 (98.1%) vaccinations were documented. N=12/1183 (1%) patients got infected with SARS-CoV2 after at least 2 doses of vaccination against COVID-19. N=1/12 (8.3%) patient got infected after 3 doses of vaccination. N=3/12 (25%) received 2 doses Vaxzev-ira (AstraZeneca), n=2/12 (16,7) patients 1st dose Vaxzevira, 2nd dose Comir-naty (Biontech), n=7/58.3%) patients two doses Comirnaty. In n=8/12 (66.7%) patients antibody levels were available. N=7/8 (87,5%) patients developed high antibody levels after 2 vaccinations. N=1/8 (21,5%) patient developed any antibodies against SARS-CoV2 after 2 doses of Comirnaty, measured ≥4 months after 2nd vaccination dose. This patient was treated with Abatacept. This patient came down with COVID-19 5 months after complete vaccination and died after long-standing highly intensive care. All other patients developed a mild to moderate course of COVID-19, without need of hospitalizing. Conclusion: There is a very high number of patients (98,1%), who got vaccinated in a real life setting of our rheumatological outpatient center. We have seen only a low number of SARS-CoV2-infections (1%). Most patients developed high antibody levels after vaccination and fortunately had a mild to moderate course of COVID-19 in case of SARS-CoV2-infection, independently from the different vaccination agents. Nevertheless, 1 patient came down with COVID-19 5 months after complete vaccination and died after long-standing highly intensive care. This patient did not develop any antibodies after vaccination. In conclusion, vaccination seems to be effective in patients with rheumatological disorders. However, we must be aware of the small group of patients without antibody development, since they are at risk to have a fatal course. Yet, antibody testing is not recommended in routine clinical care by official recommendations, largely because it is still unknown which level of antibodies predicts protection (3). The booster campaign and 3rd vaccinations will change the current state again, but a revaluation and further studies will be necessary.

19.
Annals of the Rheumatic Diseases ; 81:957-958, 2022.
Article in English | EMBASE | ID: covidwho-2009039

ABSTRACT

Background: There is still controversy about the efficacy of COVID-19 vaccination and its extent in lowering immunogenicity of Rheumatoid Arthritis (RA) patients. The guideline in whether immunosuppressive agents need to be discontinued before the vaccination is continuously updated because it is considered to lower immunogenicity. Furthermore, there is great discussion on the effectiveness of the COVID-19 booster vaccine and interest in antibody generation in different types of vaccine, as in South Korea there are many patients who were prescribed the mRNA booster vaccine after two doses of ChAdOx1-S nCoV-19 vaccine. Objectives: Thus, we investigated the differences of antibody production between patients who received only two doses of ChAdOx1-S nCoV-19 and those who received the mRNA booster vaccine. Also, antibody production under different types of immunosuppressive agents was analyzed. Methods: From October 14, 2021 to January 21, 2022 at a tertiary referral center, two patient groups diagnosed with RA were studied prospectively;one group that completed 1st and 2nd doses of ChAdOx1-S nCoV-19 vaccine, second group that completed mRNA booster vaccine as well as two doses of ChAdOx1-S nCoV-19 vaccine. SARS-CoV-2 antibody testing on the semiquantitative anti-SARS-CoV-2 S enzyme immunoassay was done, and differences in antibody titers were analyzed in patients who received different immunosup-pressive agents such as csDMARD, TNF inhibitor, JAK inhibitor, Tocilizumab, Abatacept and Corticosteroid. Statistical analysis with a multivariate logistic regression model was performed. Results: In a total of 261 patients, 153 patients had completed two doses of ChAdOx1-S nCoV-19, 108 patients had completed third mRNA booster vaccine. Anti-SARS-CoV-2 RBD antibody positive rate (titer>0.8U/mL) was 97%(149/153) and 99%(107/108) respectively, and only 5 patients showed negative result. In the aspect of high antibody titer(>250U/mL), which is the upper limit of the RBD antibody immunoassay, the result showed rate of 31% (47/153) in the non-booster group and 94%(102/108) in the booster group respectively. Among the different immunosuppressive agents and other clinical aspects, multivariate analysis revealed that corticosteroid use (OR 0.91;95% CI: 0.86-0.98), older age(OR 4.33;95% CI: 1.34-13.91), and male gender(OR 0.35;95% CI 0.16-0.75) were signifcantly associated with low rate of high antibody titer. Furthermore, out of 14 patients who underwent antibody test twice before and after the mRNA booster vaccine, other than four patients who already showed high titer of >250U/mL before the mRNA booster vaccine, 10 patients showed an increase in titer after the booster vaccine and 7 patients were acquired high titer of >250U/mL. Conclusion: Anti-SARS-CoV-2 RBD antibody positive rate was 97% or more regardless of the mRNA booster vaccination. However, patients who received the mRNA booster vaccine after two doses of ChAdOx1-S nCoV-19 vaccine showed high antibody titer (>250U/mL) three times more than those who did not receive the booster shot. Our fndings also showed that corticosteroid use, old age, and male gender is signifcantly associated with low rate of acquiring high antibody titer.

20.
Annals of the Rheumatic Diseases ; 81:1227, 2022.
Article in English | EMBASE | ID: covidwho-2009033

ABSTRACT

Background: Many patients with palindromic rheumatism (PR), mainly those with positive autoantibodies, evolve to rheumatoid arthritis (RA). Management of PR is empirical, and hydroxychloroquine (HCQ) is the most used antirheumatic drug. Abatacept (ABA) has been investigated in preclinical RA with good results. There are no randomized clinical trials in PR. Objectives: To present the design of a randomized clinical trial in PR (PALABA study). To describe the characteristics of the patients at study entry. The main objective is to test the hypothesis that ABA can reduce the progression of RA in seropositive (ACPA+ and/or RF+) PR patients in comparison with HCQ. Methods: Phase IV multicenter open label randomized controlled clinical trial with 42 months duration. The enrollment period was 18 months and the open randomized period 24 months. Fourteen spanish centers were included. The sample size was 70 patients (35 per arm). ABA sc 125 mg/week frst year, 125 mg eow second year and HCQ oral 5mg/Kg daily were administered, both therapies in monotherapy. The main inclusion criteria were age >18 years with PR according to Guerne and Weissman modifed criteria and disease evolution >3 and <36 months. Positive ACPA (ELISA or chemiluminescence (CCP2) and/or RF tests are required. Patients with arthritis in ≥1 joint >1 week at baseline, with criteria of other rheumatic diseases, radiographic erosions or previous antirheumatic therapy with synthetic DMARDS were excluded. The main outcome measure is achievement of RA classifcation criteria (EULAR/ACR 2010) at any time during the 24-month follow-up. Secondary outcomes were the number and intensity of joint attacks, adverse events, and effects on serum ACPA and anti-carbamylated antibodies at 0,3,12,24 months of follow-up. STATISTICS: Modifed Full Analysis Set and Per Protocol Population analysis. Results: Patient one was included in June 2018. The inclusion period has been extended until April 2022 due to low recruitment rates, partly due to the COVID-19 pandemic. As of 15 Jan 2022, 51 patients have been randomized and 49 (37F/12M) have received at least one drug dose. The mean onset of symptoms was 9.9±6.3 months. In 22 patients the follow-up time was greater than 12 months. RF and ACPA (CCP2) were positive in 81.6% and 89.8% of patients respectively;24 patients were included in the ABA arm and 25 in the HCQ arm. Seven patients withdrew from the study during follow-up due to: progression to RA (n=3), adverse events (n=2) and other reasons (n=2). The demographic, clinical and laboratory characteristics of PR patients at study entry are shown in Table 1. No signifcant differences in patients' characteristics between arms were observed at enrollment except a higher prevalence of CCP2 in the HCQ arm. Conclusion: We present the design of the frst randomized clinical trial in PR of the efficacy of antirheumatic drugs (ABA vs HCQ) to avoid progression towards RA in patients with a high risk (recent onset PR and positive autoantibody status) of persistent arthritis. The characteristics of patients included until now are similar to those reported in recent onset PR.

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