scholarly journals POS1226 THE COURSE OF CORONAVIRUS DISEASE 2019 (COVID-19) IN PATIENTS WITH SJOGREN’S SYNDROME TREATED WITH ANTI-CD20 MONOCLONAL ANTIBODY (RITUXIMAB)

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 896.3-897
Author(s):  
E. Sokol ◽  
A. Torgashina ◽  
B. Chalcev ◽  
J. Khvan ◽  
O. Golovina
Keyword(s):  
Monoclonal Antibody ◽  
B Cell ◽  
Rheumatic Diseases ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Lung Involvement ◽  
Anti Cd20 ◽  
Sjögren‘S Syndrome

Background:The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease 2019 (COVID-19) raised concern for the outcomes in people with different rheumatic diseases and management of these patients. There was an anxiety that biologic therapies, especially anti-B-cell depletion strategies, could lead to more severe disease course and lack of protective antibodies formation. Information about the course of COVID-19 in patients with certain rheumatic diseases is still lacking.Objectives:To examine clinical course of COVID-19 in patients with Sjogren’s syndrome treated with anti-CD20 monoclonal antibody (rituximab).Methods:Single center observational study. Diagnosis of SjS was based on ECR/EULAR 2016 criteria. COVID-19 diagnosis was based on positive PCR test even without clinical symptoms and/or typical clinical features (CT signs, fever and anosmia). Rituximab was administrated in two 1000 mg infusions 14 days apart for the 1st course, then 500 mg every 6 months.Results:19 patients were included, 18 women and 1 man. Median age was 55 years (29-70 years), and median rituximab treatment duration was 24 months (1-48 months). Five patients had concomitant RA (2 patients), SLAE (1 pt), Systemic sclerosis (2 patients). Patients with RA took baricitinib and methotrexate as well. 3 patients had MALT-lymphoma anamnesis (24, 38 and 24 months before the diagnosis of COVID-19). Only 3 patients had chronic ischemic heart disease and/or arterial hypertension. 12 patients were PCR positive, 6 negative and in 1 the test was not done. 11 patients had full and 4 partial B-cell depletion in peripheral blood. Five patients had <20% lung involvement on CT, 2 patients – 20-40% and 4 patients – 40-60%. Three patients with 40-60% lung involvement required hospitalization due to marked shortness of breath and long febrile period, 2 of them received anti-IL6 treatment and neither of them required mechanical lung ventilation (either non-invasive or invasive). Seventeen patients were treated at home and recovered in 10-24 days. Anti-SARS-CoV-2 IgG were measured in 9 patients, 6 (66.7%) of them were positive.Conclusion:It seems that neither SjS itself nor anti-CD20 therapy predisposes patients to severe course of COVID-19. Presumably risk factors such as age, diabetes or anamnesis of cardiovascular diseases have far more significant impact on COVID-19 severity. Data hints that anti-CD20 therapy might negatively affect the formation of specific anti-SARS-CoV-2 humoral immunity, but further investigation is required to determine that with any degree of certainty.Disclosure of Interests:None declared

Treatment of primary Sjögren’s syndrome with ianalumab (VAY736) targeting B cells by BAFF receptor blockade coupled with enhanced, antibody-dependent cellular cytotoxicity

2019 ◽  
Vol 78 (5) ◽  
pp. 641-647 ◽  
Author(s):  
Thomas Dörner ◽  
Maximilian Georg Posch ◽  
Yue Li ◽  
Olivier Petricoul ◽  
Maciej Cabanski ◽  
...  
Keyword(s):  
B Cell ◽  
Clinical Outcomes ◽  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Single Infusion ◽  
Sjögren‘S Syndrome

ObjectivesTo evaluate the efficacy and safety of ianalumab (VAY736), a B cell-depleting, B cell activating factor receptor-blocking, monoclonal antibody, in patients with active primary Sjögren’s syndrome (pSS) in a double-blind, placebo-controlled, phase II, single-centre study.MethodsPatients with pSS, EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) ≥6, were randomised to ianalumab single infusion at either 3 mg/kg (n=6), 10 mg/kg (n=12) or placebo (n=9). Outcomes were measured blinded at baseline and weeks 6, 12, 24, and unblinded at end of study (EoS) when B cell numbers had recovered. Clinical outcomes included ESSDAI, EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI), salivary flow rate, ocular staining score, physician global assessment and patient assessments of fatigue and general quality of life. Laboratory-based measures included circulating leucocyte subsets and markers of B cell activity.ResultsA similar trend showing positive therapeutic effect by ianalumab was observed across the primary clinical outcome (ESSDAI) and all secondary clinical outcomes (ESSPRI, Multidimensional Fatigue Inventory, Short Form-36, global assessments by physician and patient) versus the placebo-treated group. Rapid and profound B cell depletion of long-lasting duration occurred after a single infusion of ianalumab at either dose. Serum Ig light chains decreased, with return to baseline levels at EoS. Changes in some clinical outcomes persisted through to EoS in the higher dose group. Adverse effects were largely limited to mild to moderate infusion reactions within 24 hours of ianalumab administration.ConclusionsOverall results in this single-dose study suggest potent and sustained B cell depletion by ianalumab could provide therapeutic benefits in patients with pSS without major side effects.

scholarly journals A phase 2 multicenter study of ublituximab, a novel glycoengineered anti-CD20 monoclonal antibody, in patients with relapsing forms of multiple sclerosis

2020 ◽  
pp. 135245852091837 ◽  
Author(s):  
Edward Fox ◽  
Amy E Lovett-Racke ◽  
Matthew Gormley ◽  
Yue Liu ◽  
Maria Petracca ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Monoclonal Antibody ◽  
B Cell ◽  
Optimal Dose ◽  
Cell Depletion ◽  
Controlled Study ◽  
Lesion Volume ◽  
B Cell Depletion ◽  
Phase 2 ◽  
Anti Cd20

Background: Ublituximab, a novel monoclonal antibody (mAb) targeting a unique epitope on the CD20 antigen, is glycoengineered for enhanced B-cell targeting through antibody-dependent cellular cytotoxicity (ADCC). Greater ADCC may allow lower doses and shorter infusion times versus other anti-CD20 mAbs. Objective: The objective was to determine optimal dose, infusion time, and activity of ublituximab in relapsing multiple sclerosis. Methods: This is a phase 2, placebo-controlled study. Patients received three ublituximab infusions (150 mg over 1–4 hours on day 1 and 450–600 mg over 1–3 hours on day 15 and week 24) in six dosing cohorts. The primary endpoint was B-cell depletion. Results: In all cohorts ( N = 48), median B-cell depletion was >99% by week 4, maintained at weeks 24 and 48. Most common adverse events (AEs) were infusion-related reactions (all grade 1–2), with no apparent increased incidence at shorter infusion times. There were no AE-related discontinuations. At weeks 24 and 48, no T1 gadolinium-enhancing lesions ( p = 0.003) and a 10.6% decrease in T2 lesion volume ( p = 0.002) were detected. The annualized relapse rate was 0.07; 93% remained relapse free on study. Overall, 74% of patients had no evidence of disease activity (NEDA). Conclusion: Ublituximab was safely infused as rapid as 1 hour, producing robust B-cell depletion and profound reductions in magnetic resonance imaging (MRI) activity and relapses.

scholarly journals Analysis of prognostic factors in diffuse large B-cell lymphoma associated with rheumatic diseases

2021 ◽  
Vol 8 (1) ◽  
pp. e000561
Author(s):  
Vadim Gorodetskiy ◽  
Natalya Probatova ◽  
Tatiana Obukhova ◽  
Vladimir Vasilyev
Keyword(s):  
Prognostic Factors ◽  
B Cell ◽  
Rheumatic Diseases ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Large B Cell Lymphoma ◽  
Large B Cell ◽  
Sjögren‘S Syndrome

ObjectiveThe risk of developing diffuse large B-cell lymphoma (DLBCL) is increased in many rheumatic diseases (RDs). It is possible that RD-associated DLBCL is a distinct subset within the category of ‘DLBCL’, exhibiting characteristic biological features and clinical behaviour. However, information on RD-associated DLBCL is limited.MethodsWe searched the V.A. Nasonova Research Institute of Rheumatology (Russia) database from 1996 to 2021 for patients with RDs and coexisting DLBCL. Prognostic factors including the International Prognostic Index (IPI), bulk disease and c-MYC/8q24 gene rearrangements were analysed. Furthermore, we stratified DLBCLs as germinal centre B-cell (GCB) subtype and non-GCB subtype based on Hans’ immunohistochemical algorithm and also examined Epstein-Barr virus (EBV) status.ResultsTwenty-seven patients with RD-associated DLBCL were identified. Twenty patients had primary Sjogren’s syndrome, three had systemic lupus erythematosus, two had rheumatoid arthritis and two had systemic sclerosis. Secondary Sjogren’s syndrome was found in four patients. The median age at the time of diagnosis of DLBCL was 59 years with a female predominance (26:1). Based on IPI, 16 patients were assigned to the intermediate-high and high-risk groups. Bulk disease was detected in 29% of patients. Of the 20 examined cases, 4 (20%) were classified as the GCB subtype and 16 (80%) were classified as the non-GCB subtype. EBV was detected in 2 of the 21 tested cases (10%), and the c-MYC/8q24 gene rearrangement was not found in any of the 19 examined cases. After the lymphoma diagnosis, the median overall survival (OS) was 10 months (range: 0–238 months).ConclusionsExcept for the more common non-GCB subtype, we did not identify any other prognostic factor that could influence the prognosis of patients with RD-associated DLBCL. We believe that short OS in our patients was predominantly associated with decreased tolerance to lymphoma treatment.

scholarly journals Treatment of Graves’ disease and associated ophthalmopathy with the anti-CD20 monoclonal antibody rituximab: an open study

2007 ◽  
Vol 156 (1) ◽  
pp. 33-40 ◽  
Author(s):  
Mario Salvi ◽  
Guia Vannucchi ◽  
Irene Campi ◽  
Nicola Currò ◽  
Davide Dazzi ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
B Cell ◽  
Thyroid Function ◽  
Cell Depletion ◽  
Clinical Activity ◽  
Graves Disease ◽  
B Cell Depletion ◽  
Muscle Involvement ◽  
Inflammatory Phase ◽  
Anti Cd20

Introduction: Hyperthyroid Graves’ disease (GD) is a B-cell-mediated condition caused by TSH receptor antibodies (TRAb), which decline when GD remits. Anti-CD20 monoclonal antibody rituximab (RTX) induces transient B-cell depletion that may potentially modify the active inflammatory phase of thyroid-associated ophthalmopathy (TAO). Methods: Nine patients with GD, (seven with active TAO, two with mild lid signs) were studied. The trial was only approved as an open pilot study; thus we compared the effect of RTX therapy to that of i.v. glucocorticoids (IVGC) in 20 consecutive patients. Patients were treated with RTX (1000 mg i.v. twice at 2-week interval) or with IVGC (500 mg i.v. for 16 weeks). TAO was assessed by the clinical activity score (CAS) and severity was classified using NOSPECS (No signs or symptoms; Only signs (lid); Soft tissue involvement; Proptosis, Extraocular muscle involvement; Corneal involvement; Sight loss). Thyroid function and lymphocyte count were measured by standardized methods. Results: All patients attained peripheral B-cell depletion with the first RTX infusion. Minor side effects were reported in three patients. Thyroid function was not affected by RTX therapy and hyperthyroid patients required therapy with methimazole. After RTX, the changes in the levels of thyroglobulin antibodies, thyroperoxidase antibodies and TRAb were neither significant nor correlated with CD20+ depletion (P = NS). CAS values before RTX were 4.7 ± 0.5 and decreased to 1.8 ± 0.8 at the end of follow-up (P < 0.0001) and more significantly compared with IVGC (P < 0.05). Proptosis decreased significantly after RTX both in patients with active TAO (ANOVA; P < 0.0001) and those with lid signs (ANOVA; P < 0.003). The degree of inflammation (class 2) decreased significantly in response to RTX (ANOVA; P < 0.001). Relapse of active TAO was not observed in patients treated with RTX, but occurred in 10% of those treated with IVGC, who also experienced adverse effects more frequently (45 vs 33% of patients). Conclusions: RTX positively affects the clinical course of TAO, independently of either thyroid function or circulating antithyroid antibodies, including TRAb. If our findings are confirmed in large controlled studies, RTX may represent a useful therapeutic tool in patients with active TAO.

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