scholarly journals Iatrogenic antibody deficiency from B-cell targeted therapies in autoimmune rheumatic diseases

2019 ◽  
Vol 6 (1) ◽  
pp. e000337 ◽  
Author(s):  
Sonali Wijetilleka ◽  
David Jayne ◽  
Chetan Mukhtyar ◽  
Mohammed Yousuf Karim
Keyword(s):  
B Cell ◽  
Rheumatic Diseases ◽  
Targeted Therapies ◽  
Side Effect ◽  
Antineutrophil Cytoplasmic Antibody ◽  
Antibody Deficiency ◽  
Significant Group ◽  
Autoimmune Rheumatic Diseases ◽  
Increased Risk ◽  
Mild Reduction

B-cell targeted therapies (BCTT) are now widely used in autoimmune rheumatic diseases, including SLE, antineutrophil cytoplasmic antibody-associated vasculitis and rheumatoid arthritis. Early studies suggested that rituximab did not influence serum immunoglobulins. However, subsequently, with increased patient numbers, longer follow-up duration and many patients having received multiple BCTT courses, multiple subsequent studies have identified hypogammaglobulinaemia as a potential side effect. Patients developing hypogammaglobulinaemia appear to fit into two principal categories: the majority who develop transient, often mild reduction in immunoglobulins without increased infection and a much smaller but clinically significant group with a more sustained antibody deficiency, who display increased risk of infection. Monitoring immunoglobulin levels represents an opportunity for the early detection of hypogammaglobulinaemia, and the prevention of avoidable morbidity. In the two major studies, approximately 4%–5% of BCTT-treated patients required immunoglobulin replacement due to recurrent infections in the context of hypogammaglobulinaemia. Despite this, monitoring of immunoglobulins is suboptimal, and there remains a lack of awareness of hypogammaglobulinaemia as an important side effect.

scholarly journals Recommendations for the management of secondary hypogammaglobulinaemia due to B cell targeted therapies in autoimmune rheumatic diseases

Rheumatology ◽  
2018 ◽  
Vol 58 (5) ◽  
pp. 889-896 ◽  
Author(s):  
Sonali Wijetilleka ◽  
David R Jayne ◽  
Chetan Mukhtyar ◽  
Aftab Ala ◽  
Philip D Bright ◽  
...  
Keyword(s):  
B Cell ◽  
Replacement Therapy ◽  
Rheumatic Diseases ◽  
Targeted Therapies ◽  
Health Care Professionals ◽  
Clinical Decision Making ◽  
British Society ◽  
Immunoglobulin Replacement Therapy ◽  
Autoimmune Rheumatic Diseases ◽  
Immunoglobulin Replacement

Abstract Objectives The association of B cell targeted therapies with development of hypogammaglobulinaemia and infection is increasingly recognized. Our aim was to develop consensus recommendations for immunoglobulin replacement therapy for management of hypogammaglobulinaemia following B cell targeted therapies in autoimmune rheumatic diseases. Methods A modified Delphi exercise involved a 17-member Taskforce committee, consisting of immunologists, rheumatologists, nephrologists, haematologists, a gastroenterologist, an immunology specialist nurse and a patient representative. The first round identified the most pertinent topics to address in the recommendations. A search string was agreed upon for the identification of publications in PubMed focusing on these areas, for a systematic literature review. Original data was presented from this review to the Taskforce committee. Recommendations from the British Society for Rheumatology, the UK Department of Health, EULAR, the ACR, and the American Academy of Allergy, Asthma, and Immunology were also reviewed. The evidence was discussed in a face-to-face meeting to formulate recommendation statements. The levels of evidence and statements were graded according to Scottish Intercollegiate Guidelines Network methodology. Results Three overarching principles, eight recommendation statements and a research agenda were formulated. The Taskforce committee voted on these statements, achieving 82–100% agreement for each recommendation. The strength of the recommendations was restricted by the low quality of the available evidence, with no randomized controlled trial data. The recommendations cover risk factors, monitoring, referral for hypogammaglobulinaemia; indications, dosage and discontinuation of immunoglobulin replacement therapy. Conclusion These are the first recommendations specifically formulated for B cell targeted therapies related to hypogammaglobulinaemia in autoimmune rheumatic diseases. The recommendations are to aid health-care professionals with clinical decision making for patients with hypogammaglobulinaemia.

B cell checkpoints in autoimmune rheumatic diseases

2019 ◽  
Vol 15 (5) ◽  
pp. 303-315 ◽  
Author(s):  
Samuel J. S. Rubin ◽  
Michelle S. Bloom ◽  
William H. Robinson
Keyword(s):  
B Cell ◽  
Rheumatic Diseases ◽  
Autoimmune Rheumatic Diseases

scholarly journals B cell depletion in immune-mediated rheumatic diseases and coronavirus disease 2019 (COVID-19)

2021 ◽  
Vol 59 (4) ◽  
pp. 384-393
Author(s):  
E. L. Nasonov ◽  
A. S. Avdeeva
Keyword(s):  
B Cell ◽  
Rheumatic Diseases ◽  
Bacterial Infections ◽  
Human Monoclonal Antibody ◽  
Chimeric Mouse ◽  
Internal Organs ◽  
Irreversible Damage ◽  
Autoimmune Rheumatic Diseases ◽  
Number Of Factors ◽  
Immune Mediated

In patients with immune-mеdiated (autoimmune) rheumatic diseases (IMIRD), there are a number of factors (advanced age, uncontrolled inflammation, initially irreversible damage to internal organs, comorbid pathology, genetic and other factors) that can potentially lead to an increase in “sensitivity” to SARS-CoV -2 (severe acute respiratory syndrome coronavirus-2) and concomitant viral and bacterial infections, an increase in the risk of a severe course of COVID-19 (coronavirus disease 2019), a decrease in the effectiveness of therapy for both IMIRDs and COVID-19. An important area of pharmacotherapy for IMIRDs and other autoimmune diseases is associated with the use of anti-B-cell drugs, primarily rituximab (RTX), which is a chimeric (mouse/human) monoclonal antibody (mAb) to the CD20 antigen of B cells. At present, in Russia, the RTM biosimilar, acellbia (BIOCAD), is widely used, which is not inferior to RTX in terms of efficiency and safety. The problems of anti-B-cell therapy during the COVID-19 pandemic in relation to the risk of infection, severe course and insufficient effectiveness of vaccination against SARSCoV- 2 are considered. According to the recommendations of the Association of Rheumatologists of Russia, a more rigorous assessment of indications for induction and maintenance therapy of RTX therapy and harmonization of the timing of drug administration and vaccination is required.

scholarly journals Role of targeted therapies in rheumatic patients on COVID-19 outcomes: results from the COVIDSER study

RMD Open ◽  
2021 ◽  
Vol 7 (3) ◽  
pp. e001925
Author(s):  
Jose María Álvaro Gracia ◽  
Carlos Sanchez-Piedra ◽  
Javier Manero ◽  
María Ester Ruiz-Lucea ◽  
Laura López-Vives ◽  
...  
Keyword(s):  
Rheumatic Disease ◽  
Rheumatic Diseases ◽  
Targeted Therapies ◽  
Disease Diagnosis ◽  
Sociodemographic Factors ◽  
Inflammatory Rheumatic Diseases ◽  
Increased Risk ◽  
Related Hospitalisation ◽  
Observational Cohort ◽  
Synthetic Dmards

ObjectivesTo analyse the effect of targeted therapies, either biological (b) disease-modifying antirheumatic drugs (DMARDs), targeted synthetic (ts) DMARDs and other factors (demographics, comorbidities or COVID-19 symptoms) on the risk of COVID-19 related hospitalisation in patients with inflammatory rheumatic diseases.MethodsThe COVIDSER study is an observational cohort including 7782 patients with inflammatory rheumatic diseases. Multivariable logistic regression was used to estimate ORs and 95% CIs of hospitalisation. Antirheumatic medication taken immediately prior to infection, demographic characteristics, rheumatic disease diagnosis, comorbidities and COVID-19 symptoms were analysed.ResultsA total of 426 cases of symptomatic COVID-19 from 1 March 2020 to 13 April 2021 were included in the analyses: 106 (24.9%) were hospitalised and 19 (4.4%) died. In multivariate-adjusted models, bDMARDs and tsDMARDs in combination were not associated with hospitalisation compared with conventional synthetic DMARDs (OR 0.55, 95% CI 0.24 to 1.25 of b/tsDMARDs, p=0.15). Tumour necrosis factor inhibitors (TNF-i) were associated with a reduced likelihood of hospitalisation (OR 0.32, 95% CI 0.12 to 0.82, p=0.018), whereas rituximab showed a tendency to an increased risk of hospitalisation (OR 4.85, 95% CI 0.86 to 27.2). Glucocorticoid use was not associated with hospitalisation (OR 1.69, 95% CI 0.81 to 3.55). A mix of sociodemographic factors, comorbidities and COVID-19 symptoms contribute to patients’ hospitalisation.ConclusionsThe use of targeted therapies as a group is not associated with COVID-19 severity, except for rituximab, which shows a trend towards an increased risk of hospitalisation, while TNF-i was associated with decreased odds of hospitalisation in patients with rheumatic disease. Other factors like age, male gender, comorbidities and COVID-19 symptoms do play a role.

scholarly journals The Effect of Statin Use on Mortality in Systemic Autoimmune Rheumatic Diseases

2018 ◽  
Vol 45 (12) ◽  
pp. 1689-1695 ◽  
Author(s):  
April M. Jorge ◽  
Na Lu ◽  
Sarah F. Keller ◽  
Sharan K. Rai ◽  
Yuqing Zhang ◽  
...  
Keyword(s):  
General Population ◽  
Propensity Score ◽  
Rheumatic Diseases ◽  
Lupus Erythematosus ◽  
Antineutrophil Cytoplasmic Antibodies ◽  
Autoimmune Rheumatic Diseases ◽  
Premature Cardiovascular Disease ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Statin Use

Objective.Systemic autoimmune rheumatic diseases (SARD) are associated with an increased risk of premature cardiovascular disease (CVD) and all-cause mortality. We examined the potential survival benefit of statin use among patients with SARD in a general population setting.Methods.We conducted an incident user cohort study using a UK general population database. Our population included patients with a SARD as determined by Read code diagnoses of systemic lupus erythematosus, systemic sclerosis, Sjögren syndrome, dermatomyositis, polymyositis, mixed connective tissue disease, Behçet disease, or antineutrophil cytoplasmic antibodies-associated vasculitis between January 1, 2000, and December 31, 2014. We compared propensity score–matched cohorts of statin initiators and noninitiators within 1-year cohort accrual blocks to account for potential confounders, including disease duration, body mass index, lifestyle factors, comorbidities, and medication use.Results.Of 2305 statin initiators, 298 died during the followup period (mean 5.1 yrs), whereas among 2305 propensity score–matched noninitiators, 338 died during the followup period (mean 4.8 yrs). This corresponded to mortality rates of 25.4/1000 and 30.3/1000 person-years, respectively. Statin initiation was associated with reduced all-cause mortality (HR 0.84, 95% CI 0.72–0.98). When we compared the unmatched cohorts, the statin initiators (n = 2863) showed increased mortality (HR 1.85, 95% CI 1.58–2.16) compared with noninitiators (n = 2863 randomly selected within 1-year cohort accrual blocks) because of confounding by indication.Conclusion.In this general population–based study, statin initiation was shown to reduce overall mortality in patients with SARD after adjusting for relevant determinates of CVD risk.

B cell depletion in autoimmune rheumatic diseases

2005 ◽  
Vol 4 (7) ◽  
pp. 436-441 ◽  
Author(s):  
Milena Pitashny ◽  
Yehuda Shoenfeld
Keyword(s):  
B Cell ◽  
Rheumatic Diseases ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Autoimmune Rheumatic Diseases

Factors Associated with Incident Severe Pulmonary Arterial Hypertension in Systemic Autoimmune Rheumatic Diseases: a Nationwide Study

Rheumatology ◽  
2021 ◽  
Author(s):  
Hsin-Hua Chen ◽  
Ching-Heng Lin ◽  
Tsu-Yi Hsieh ◽  
Der-Yuan Chen ◽  
Jia-Ching Ying ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Rheumatic Diseases ◽  
Lupus Erythematosus ◽  
Conditional Logistic Regression ◽  
Factors Associated ◽  
Autoimmune Rheumatic Diseases ◽  
Increased Risk ◽  
Pulmonary Arterial ◽  
Severe Pulmonary Arterial Hypertension

Abstract Objectives To assess the association of severe pulmonary arterial hypertension (PAH) with particulate matter <2.5 μm (PM2.5) and clinical data in patients with systemic autoimmune rheumatic diseases (SARDs). Methods We used the 2003–2017 nationwide data in Taiwan to identify patients with SARDs, including systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, dermatomyositis/polymyositis and primary Sjögren’s syndrome. We identified 479 cases with severe PAH and selected controls matched (1:4) for age, sex, and index-year. We used conditional logistic regression analysis to determine factors associated with risks for severe PAH shown as odds ratios (ORs) with 95% confidence intervals (CIs). Results We found that severe PAH was highly associated with interstitial lung disease (OR, 8.57; 95% CI, 5.52–13.32), congestive heart failure (OR, 7.62; 95% CI, 5.02–11.55), valvular heart disease (OR, 3.34; 95% CI, 2.03–5.50) and slightly associated with thyroid diseases (OR, 1.88; 95% CI, 1.18–3.00), but not the level of exposure to PM2.5. Increased risk for PAH was found in patients receiving corticosteroid (prednisolone equivalent dosage, mg/day, OR, 1.03; 95% CI, 1.01–1.05), biologics (OR, 2.18; 95% CI, 1.15–4.12) as well as immunosuppressants, including cyclosporin (OR, 2.17; 95% CI, 1.31–3.59), azathioprine (OR, 1.96; 95% CI, 1.48–2.61), cyclophosphamide (OR, 2.01; 95% CI, 1.30–3.11) and mycophenolate mofetil/mycophenolic acid (OR, 2.42; 95% CI, 1.37–4.27), and those with the highest level of insured amount (reference, lowest level; OR, 0.53; 95% CI, 0.34–0.83). Conclusion The population-based study identified risks for severe PAH in patients with SARDs, and these findings provide evidence for PAH risk stratification in patients with SARDs.

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