ABSTRACT
Autoimmune hemolytic anemia (AIHA) is defined by increased erythrocyte turnover mediated by autoimmune mechanisms. While corticosteroids remain first-line therapy in most cases of warm-antibody AIHA, cold agglutinin disease is treated by targeting the underlying clonal B-cell proliferation or the classical complement activation pathway. Several new established or investigational drugs and treatment regimens have appeared during the last 1-2 decades, resulting in an improvement of therapy options but also raising challenges on how to select the best treatment in individual patients. In severe warm-antibody AIHA, there is evidence for the upfront addition of rituximab to prednisolone in the first line. Novel agents targeting B-cells, extravascular hemolysis, or removing IgG will offer further options in the acute and relapsed/refractory settings. In cold agglutinin disease, the development of complement inhibitors and B-cell targeting agents makes it possible to individualize therapy, based on the disease profile and patient characteristics. For most AIHAs, the optimal treatment remains to be found, and there is still a need for more evidence-based therapies. Therefore, prospective clinical trials should be encouraged.
Subject(s)
Anemia, Hemolytic, Autoimmune , Humans , Anemia, Hemolytic, Autoimmune/drug therapy , Prospective Studies , Rituximab/therapeutic use , Adrenal Cortex Hormones/therapeutic use , HemolysisABSTRACT
Background: Humoral and cellular immune responses are known to be crucial for patients to recover from COVID-19 and to protect them against SARS-CoV-2 reinfection once infected or vaccinated. Objectives: This study aimed to investigate humoral and T cell responses to SARS-CoV-2 vaccination in patients with autoimmune diseases after the second and third vaccine doses while on rituximab and their potential protective role against reinfection. Methods: Ten COVID-19-naïve patients were included. Three time points were used for monitoring cellular and humoral responses: pre-vaccine to exclude virus exposure (time point 1) and post-second and post-third vaccine (time points 2 and 3). Specific IgG antibodies were monitored by Luminex and T cells against SARS-CoV-2 spike-protein by ELISpot and CoVITEST. All episodes of symptomatic COVID-19 were recorded. Results: Nine patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis and one with an undifferentiated autoimmune disease were included. Nine patients received mRNA vaccines. The last rituximab infusion was administered for a mean (SD) of 15 (10) weeks before the first vaccine and six patients were CD19-B cell-depleted. After a mean (SD) of 19 (10) and 16 (2) days from the second and third vaccine dose, IgG anti-SARS-CoV-2 antibodies were detected in six (60%) and eight (80%) patients, respectively. All patients developed specific T cell responses by ELISpot and CoVITEST in time points 2 and 3. Previous B cell depletion correlated with anti-SARS-CoV-2 IgG levels. Nine (90%) patients developed mild COVID-19 after a median of 7 months of the third dose. Conclusion: Rituximab in patients with autoimmune diseases reduces humoral responses but does not avoid the development of T cell responses to SARS-CoV-2 vaccination, which remain present after a booster dose. A steady cellular immunity appears to be protective against subsequent reinfections.
Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis , Autoimmune Diseases , COVID-19 , Humans , SARS-CoV-2 , COVID-19 Vaccines , Reinfection , Rituximab/therapeutic use , T-Lymphocytes , Vaccination , Autoimmune Diseases/drug therapy , Immunoglobulin G , Antibodies, ViralABSTRACT
Background: Myasthenia gravis (MG) is an immune-mediated disorder of the neuromuscular junction. About 10% are refractory to immunosuppressive therapy. Aims: To analyze the response of patients with generalized MG to rituximab. Methods and Materials: A retrospective review of patients with MG who received rituximab was carried out (n = 13, M:F = 6:7, mean age: 44.84 ± 15.73 years). Myasthenia Gravis Foundation of America (MGFA), MGFA post-intervention status (MGFA-PIS), and Myasthenia Gravis Status and Treatment Intensity (MGSTI) were assessed before and after rituximab. Results: The duration of MG was 104.07 ± 92.25 months. Before rituximab, the MGFA was IIA/IIB/IIIA/IIIB/IVB/V in 1/1/2/6/2/1 patients and MGSTI was four in eight patients and six in three patients. The mean duration of follow up was 20.92 ± 14.06 months (range, 4 to 42 months). Dose reduction or discontinuation of cholinesterase inhibitors could be achieved 12 patients. Complete stable remission (CSR) and pharmacologic remission (PR) were achieved in one and four patients respectively and five patients had minimal manifestations. Most patients attained level 0, 1 or 2 MGSTI at last follow up. No rituximab infusion-related adverse events were noted. Three patients had exacerbation of MG between one to five weeks after rituximab administration. Three patients died, one each due to a cardiac event unrelated to MG or treatment, complications related to myasthenic crisis, and coronavirus disease. Conclusions: Rituximab was effective in bringing about remission in MG and can be considered as a first-line agent. However, it has to be administered under close supervision as some patients develop exacerbation of MG akin to steroid-induced worsening.
Subject(s)
Developing Countries , Myasthenia Gravis , Humans , Adult , Middle Aged , Rituximab/therapeutic use , Treatment Outcome , Myasthenia Gravis/drug therapy , Retrospective StudiesABSTRACT
Serologic responses of COVID-19 vaccine are impaired in patients with B-cell lymphoma, especially those who had recently been treated with anti-CD20 monoclonal antibodies. However, it is still unclear whether those patients develop an immune response following vaccination. We investigated the efficacy of vaccination against SARS-CoV-2 in 171 patients with B-cell non-Hodgkin lymphoma (B-NHL) who received two doses of an mRNA-based COVID-19 vaccine and we compared the efficacy of vaccination to that in 166 healthy controls. Antibody titers were measured 3 months after administration of the second vaccine dose. Patients with B-NHL showed a significantly lower seroconversion rate and a lower median antibody titer than those in healthy controls. The antibody titers showed correlations with the period from the last anti-CD20 antibody treatment to vaccination, the period from the last bendamustine treatment to vaccination and serum IgM level. The serologic response rates and median antibody titers were significantly different between diffuse large B-cell lymphoma (DLBCL) patients in whom anti-CD20 antibody treatment was completed within 9 months before vaccination and follicular lymphoma (FL) patients in whom anti-CD20 antibody treatment was completed within 15 months before vaccination. Moreover, the serologic response rates and median antibody titers were significantly different among FL patients in whom bendamustine treatment was completed within 33 months before vaccination. We demonstrated that B-NHL patients who were recently treated with anti-CD20 antibodies and bendamustine had a diminished humoral response to COVID-19 vaccination. UMIN 000,045,267.
Subject(s)
COVID-19 , Lymphoma, Follicular , Lymphoma, Large B-Cell, Diffuse , Humans , Rituximab/therapeutic use , Bendamustine Hydrochloride/therapeutic use , COVID-19 Vaccines , Immunity, Humoral , Antibodies, Monoclonal, Murine-Derived/therapeutic use , COVID-19/prevention & control , SARS-CoV-2 , Neoplasm Recurrence, Local , Lymphoma, Follicular/drug therapy , Lymphoma, Large B-Cell, Diffuse/drug therapy , Vaccination , Antibodies, ViralABSTRACT
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, ViralABSTRACT
Relapsing or occurring de novo autoimmune hemolytic anemia (AIHA) during pregnancy or puerperium is a poorly described condition. Here, we report 45 pregnancies in 33 women evaluated at 12 centers from 1997 to 2022. Among the 20 women diagnosed with AIHA before pregnancy, 10 had a relapse. An additional 13 patients developed de novo AIHA during gestation/puerperium (2 patients had AIHA relapse during a second pregnancy). Among 24 hemolytic events, anemia was uniformly severe (median Hb, 6.4 g/dL; range, 3.1-8.7) and required treatment in all cases (96% steroids ± intravenous immunoglobulin, IVIG, 58% transfusions). Response was achieved in all patients and was complete in 65% of the cases. Antithrombotic prophylaxis was administered to 8 patients (33%). After delivery, rituximab was administered to 4 patients, and cyclosporine was added to 1 patient. The rate of maternal complications, including premature rupture of membranes, placental detachment, and preeclampsia, was 15%. Early miscarriages occurred in 13% of the pregnancies. Fetal adverse events (22% of cases) included respiratory distress, fetal growth restriction, preterm birth, AIHA of the newborn, and 2 perinatal deaths. In conclusion, the occurrence of AIHA does not preclude the ability to carry out a healthy pregnancy, provided close monitoring, prompt therapy, and awareness of potential maternal and fetal complications.
Subject(s)
Anemia, Hemolytic, Autoimmune , Premature Birth , Humans , Female , Infant, Newborn , Pregnancy , Anemia, Hemolytic, Autoimmune/epidemiology , Anemia, Hemolytic, Autoimmune/therapy , Anemia, Hemolytic, Autoimmune/diagnosis , Placenta , Premature Birth/drug therapy , Rituximab/therapeutic use , Immunoglobulins, Intravenous/therapeutic use , Postpartum PeriodABSTRACT
The immune system plays a significant role in multiple sclerosis. While MS was historically thought to be T cell-mediated, multiple pieces of evidence now support the view that B cells are essential players in multiple sclerosis pathogenic processes. High-efficacy disease-modifying therapies that target the immune system have emerged over the past two decades. Anti-CD20 monoclonal antibodies selectively deplete CD20+ B and CD20+ T cells and efficiently suppress inflammatory disease activity. These monotherapies prevent relapses, reduce new or active magnetic resonance imaging brain lesions, and lessen disability progression in patients with relapsing multiple sclerosis. Rituximab, ocrelizumab, and ofatumumab are currently used in clinical practice, while phase III clinical trials for ublituximab have been recently completed. In this review, we compare the four anti-CD20 antibodies in terms of their mechanisms of action, routes of administration, immunological targets, and pharmacokinetic properties. A deeper understanding of the individual properties of these molecules in relation to their efficacy and safety profiles is critical for their use in clinical practice.
Subject(s)
Antigens, CD20 , Immunologic Factors , Multiple Sclerosis , Humans , Antigens, CD20/immunology , B-Lymphocytes/drug effects , B-Lymphocytes/immunology , Multiple Sclerosis/drug therapy , Multiple Sclerosis/immunology , Recurrence , Rituximab/therapeutic use , Rituximab/pharmacology , Immunologic Factors/pharmacology , Immunologic Factors/therapeutic use , Antibodies, Monoclonal/pharmacology , Antibodies, Monoclonal/therapeutic use , T-Lymphocytes/drug effects , T-Lymphocytes/immunologyABSTRACT
INTRODUCTION: Diffuse large B-cell lymphoma (DLBCL) is a high grade non-Hodgkin lymphoma which is common among immunodeficient people. Derangements of peripheral blood immune cells have been described to have a prognostic impact in DLBCL in high income countries, including a monocytosis, the ratios of lymphocytes to both monocytes (L:M) and neutrophils (N:L), as well as the numbers of regulatory T-cells (Tregs) and immunosuppressive monocytes (HLA-DRlow monos). To date, the impact of these variables has not been assessed in the setting of HIV-associated DLBCL (HIV-DLBCL), which is among the most common malignancies seen in people living with HIV. In this study, we assessed these factors in a cohort of South African patients with DLBCL and a high HIV-seropositivity-rate. In addition, we evaluated the prognostic value of monocyte activation (as reflected by monocyte fluorescence (MO-Y) on a Sysmex haematology analyser). This parameter has to date not been assessed in the setting of DLBCL. METHODS: A full blood count and differential count as well as flow cytometry for HLA-DRlow monocyte and Treg enumeration were performed in patients with incident DLBCL referred to the Chris Hani Baragwanath Academic Hospital in Johannesburg, South Africa between November 2019 and May 2022. Additional clinical and laboratory data were recorded from the patient charts and laboratory information system. RESULTS: Seventy-six patients were included, of whom 81.3% were people living with HIV with a median CD4 count of 148 cells/ul. Most patients had advanced stage disease (74.8%) and were predominantly treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-based chemotherapy (without Rituximab). At a median follow-up period of 19 months, the median survival time was 3.5 months, with a 12-month survival rate of 27.0%. All of the immune-cell-related variables (with the exception of the CD4 count) were similar between the people living with HIV and the HIV-negative individuals. In contrast to previous studies, a high monocyte count, the L:M and increased numbers of HLA-DRlow monocytes were not significantly associated with survival in HIV-DLBCL, while a neutrophilia (>8 x 109/L), the N:L (>6:1), high numbers of Tregs (≥5.17% of CD4s) and lymphopenia (<1.3 x 109/L) were. In addition, increased monocyte fluorescence (MO-Y >115.5) was associated with superior outcomes, which we speculate to reflect a more robust antitumour immune response among individuals with high levels of monocyte activation. On Cox Proportional hazard analysis, immune-cell factors independently associated with survival included a CD4 count <150 cells/ul and a neutrophilia. CONCLUSION: The monocyte count, L:M and the number of HLA-DRlow monos are not strong prognostic indicators in HIV-DLBCL, while a low CD4 count and neutrophilia are. Elevation of the MO-Y shows some promise as a potential biomarker of antitumour immunity; further study in this regard would be of interest.
Subject(s)
HIV Infections , Lymphoma, Large B-Cell, Diffuse , Monocytes , Humans , Antibodies, Monoclonal, Murine-Derived/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , HIV Infections/complications , Leukocyte Count , Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, Large B-Cell, Diffuse/pathology , Monocytes/immunology , Monocytes/metabolism , Prednisone/therapeutic use , Prognosis , Rituximab/therapeutic use , South Africa/epidemiology , Vincristine/therapeutic use , FluorescenceABSTRACT
BACKGROUND: Immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura are both causes of thrombocytopenia. Recognizing thrombotic thrombocytopenic purpura is crucial for subsequent treatment and prognosis. In clinical practice, corticosteroids and rituximab can be used to treat both immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura; plasma exchange therapy is the first-line treatment in thrombotic thrombocytopenic purpura, while corticosteroids are strongly recommended as first-line treatment in immune thrombocytopenic purpura. The differential diagnosis of immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura is essential in clinical practice. However, case reports have suggested that immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura can occur concurrently. CASE PRESENTATION: We report the case of a 32-year-old Asian female without previous disease who presented with pancytopenia, concurrent with immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura. The morphology of the megakaryocytes in the bone marrow indicated immune-mediated thrombocytopenia. The patient received glucocorticoid treatment, and her platelet count increased; however, schistocytes remained high during the course of the therapy. Further investigations revealed ADAMTS13 activity deficiency and positive ADAMTS13 antibodies. The high titer of antinuclear antibody and positive anti-U1-ribonucleoprotein/Smith antibody indicated a potential autoimmune disease. However, the patient did not fulfill the current criteria for systemic lupus erythematosus or mixed connective tissue disease. The patient responded well to plasma exchange therapy, and her platelet count remained normal on further follow-up. CONCLUSIONS: Concurrence of immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura is rare, but clinicians should be aware of this entity to ensure prompt medical intervention. Most of the reported cases involve young women. Human immunodeficiency virus infection, pregnancy, and autoimmune disease are the most common underlying conditions.
Subject(s)
Lupus Erythematosus, Systemic , Purpura, Thrombocytopenic, Idiopathic , Purpura, Thrombotic Thrombocytopenic , Pregnancy , Female , Humans , Adult , Purpura, Thrombotic Thrombocytopenic/diagnosis , Purpura, Thrombocytopenic, Idiopathic/complications , Platelet Count , Rituximab/therapeutic use , Lupus Erythematosus, Systemic/complicationsABSTRACT
BACKGROUND: The clinical outcomes of ABO-incompatible (ABOi) kidney transplantation have improved with the introduction of desensitization therapy with rituximab. However, rituximab prevents not only antibody-mediated rejection (AMR) but also increases the risk of adverse events, such as infection. For ABOi kidney transplantation in patients with low anti-A/B antibody titers, we previously used a rituximab-free desensitization protocol and then initiated a single dose of 100 mg rituximab in 2016. We retrospectively compared the outcomes of ABOi kidney transplantation in patients with low anti-A/B antibody titers before and after the introduction of rituximab. METHODS: ABOi kidney transplantations (n = 142) in patients with low anti-A/B antibody titers between 2007 and 2021 were included. Patients were divided into two groups (with and without rituximab) for desensitization. The primary outcomes were the incidence of acute AMR and infection. RESULTS: Sixty-six patients were desensitized without rituximab (rituximab-free group), and 76 were pretreated with 100 mg rituximab (rituximab group) before transplantation. The incidence of acute AMR was significantly lower in the rituximab group than in the rituximab-free group (.0% [0/76] vs. 7.6% [5/66], respectively; p = .047). Post-transplantation anti-A/B antibody titers were also lower in the rituximab group than in the rituximab-free group. There was no significant difference in the incidence of adverse events, including infections, between the two groups. CONCLUSION: In ABOi kidney transplantation patients with low anti-A/B antibody titers, the desensitization protocol with a single dose of 100 mg rituximab was effective in preventing acute AMR without increasing the risk of other adverse events.
Subject(s)
Kidney Transplantation , Humans , Rituximab/therapeutic use , Kidney Transplantation/adverse effects , Kidney Transplantation/methods , Retrospective Studies , Treatment Outcome , Antibodies , Blood Group Incompatibility , ABO Blood-Group System , Graft Rejection/drug therapy , Graft Rejection/etiology , Graft Rejection/epidemiology , Graft Survival , Living DonorsABSTRACT
Bendamustine and rituximab (BR) is a preferred first-line therapy for indolent non-Hodgkin's lymphoma (iNHL) and mantle cell lymphoma (MCL); however, few reports on BR performance in elderly patients are available to date. We compared safety and efficacy of BR in patients ≥70 years (elderly) vs <70 years (younger) treated at our institution. Among 201 patients, 113 were elderly (median age: 77 years), including 38 patients ≥80 years, and 88 were younger (median age: 62 years). Elderly patients had more bone marrow involvement by lymphoma, anemia, ECOG status 3 and high-risk disease follicular lymphoma (P < .05 for all). Fifty-four percent of elderly received full dose of bendamustine vs 79.5% of younger patients. More elderly patients (54%) vs younger (43.2%) experienced treatment delay. Less elderly proceeded to rituximab maintenance. Overall, the number of adverse events per patient and transformed B-Cell lymphoma/secondary malignancies were similar between groups. Elderly patients had less febrile neutropenia, rituximab-associated infusion reactions, but more herpes zoster reactivation. There were more deaths in the elderly (37.2%) vs younger (10.2%) groups (P < .001), mainly due to non-lymphoma-related causes. With median follow-up of 42 months [4.0-97.0] disease-free survival for the elderly was similar to younger patients. There was no difference between patients <80 and ≥80 years (P = .274). In conclusion, the real-world elderly patients have more advanced disease and higher ECOG status. BR is well-tolerated; elderly patients had lower incidence of febrile neutropenia. Dose reduction and treatment delays are common, but BR efficacy was not affected even in very old patients (≥80 years).
Subject(s)
Febrile Neutropenia , Lymphoma, Mantle-Cell , Lymphoma, Non-Hodgkin , Humans , Adult , Aged , Middle Aged , Rituximab/therapeutic use , Lymphoma, Mantle-Cell/drug therapy , Bendamustine Hydrochloride/adverse effects , Lymphoma, Non-Hodgkin/etiology , Febrile Neutropenia/drug therapy , Febrile Neutropenia/etiology , Antineoplastic Combined Chemotherapy Protocols/adverse effectsABSTRACT
BACKGROUND: Patients with rheumatic disease may mount a suboptimal serologic response to COVID-19 vaccination. We evaluated predictors of low antibody response in a clinic-based cohort. METHODS: We conducted a cross-sectional study using electronic health record (EHR) data at Brigham and Women's Hospital, Boston, MA. Patients with systemic rheumatic disease that had SARS-CoV-2 spike antibody (Ab) tested using the Roche Elecsys immunoassay, February-August 2021, after 2 doses of mRNA vaccine or 1 dose of adenovirus vector vaccine were identified. Demographics, systemic rheumatic disease, vaccination dates, and disease-modifying antirheumatic drugs (DMARDs) were extracted. The primary outcome was low spike Ab (≤ 200 U/mL). Logistic regression models estimated predictors of low spike Ab. RESULTS: Among 382 patients, the mean age was 57 years, 77% were female, and 37% had low spike Ab. Older age (OR 1.03, 95% CI [1.02, 1.05]), SLE (OR 4.81 [2.08, 8.43], reference: inflammatory arthritis), prednisone (OR 1.67 [1.03, 2.74]), and rituximab (OR 22.91 [9.85, 53.29]) were significantly associated with higher odds of low spike Ab. Use of csDMARD monotherapy (OR 0.12 [0.04, 0.33]) and JAK inhibitors (OR 0.41 [0.18, 0.92]) were associated with significantly lower odds for low spike Ab. After adjusting for systemic rheumatic disease and DMARDs, SLE and rituximab remained significantly associated with low spike Ab. CONCLUSIONS: Over a third of patients with systemic rheumatic disease with spike Ab tested in routine care had low spike Ab after 2 doses of mRNA or 1 dose of adenovirus vector COVID-19 vaccine. SLE and rituximab were significant risk factors for low spike Ab. KEY POINTS: ⢠More than one-third of patients with systemic rheumatic disease that had spike Ab tested in routine care had low spike Ab after 2 doses of mRNA or 1 dose of adenovirus vector COVID-19 vaccine. ⢠Diagnosis of SLE, use of prednisone, and use of rituximab were significantly associated with greater odds of low spike antibodies. ⢠These data underscore the importance of additional doses of COVID-19 vaccine and prophylactic Evusheld in immunosuppressed patients with systemic rheumatic disease as recommended by the US Centers for Disease Control.
Subject(s)
Antirheumatic Agents , COVID-19 , Lupus Erythematosus, Systemic , Humans , Female , Middle Aged , Male , COVID-19 Vaccines , Rituximab/therapeutic use , Antibody Formation , Cross-Sectional Studies , Prednisone , COVID-19/prevention & control , SARS-CoV-2 , Vaccination , Antirheumatic Agents/therapeutic use , Antibodies, ViralABSTRACT
Importance: Rituximab and other B-cell-depleting therapies blunt humoral responses to SARS-CoV-2 vaccines, particularly when the vaccine is administered within 6 months of an infusion. Whether this translates into an increased risk of hospitalization or death from COVID-19 is unclear. Objectives: To examine whether rituximab treatment is associated with an increased risk of hospitalization for COVID-19 among SARS-CoV-2-vaccinated persons with multiple sclerosis (MS) and whether delaying vaccination more than 6 months after rituximab treatment is associated with decreased risk. Design, Setting, and Participants: This retrospective cohort study used Kaiser Permanente Southern California's electronic health record to identify individuals from January 1, 2020, to February 15, 2022, who had MS and who had been vaccinated against SARS-CoV-2. Exposures: Rituximab treatment compared with disease-modifying therapies (DMTs) that do not interfere with vaccine efficacy or being untreated (no or other DMT group). Among rituximab-treated patients, the exposure was receiving at least 1 vaccine dose more than 6 months after their last infusion compared with receiving all vaccine doses 6 months or less since their last infusion. Main Outcomes and Measures: The main outcome was hospitalization due to COVID-19 infection. The odds of infection resulting in hospitalization following SARS-CoV-2 vaccination were adjusted for race and ethnicity, advanced MS-related disability; vaccine type; booster dose; and, among rituximab-treated only analyses, cumulative rituximab dose and dose at last infusion. Exposures, outcomes, and covariates were collected from the electronic health record. Results: Among 3974 SARS-CoV-2-vaccinated people with MS (mean [SD] age, 55.3 [15] years; 2982 [75.0%] female; 103 [2.6%] Asian or Pacific Islander; 634 [16.0%] Black; 953 [24.0%] Hispanic; 2269 [57.1%] White; and 15 [0.3%] other race or ethnicity), rituximab-treated patients (n = 1516) were more likely to be hospitalized (n = 27) but not die (n = 0) compared with the 2458 individuals with MS receiving no or other DMTs (n = 7 and n = 0, respectively; adjusted odds ratio [aOR] for hospitalization, 7.33; 95% CI, 3.05-17.63). Receiving messenger RNA (mRNA) SARS-CoV-2 vaccine (aOR, 0.36; 95% CI, 0.15-0.90; P = .03) and receiving a booster vaccination (aOR, 0.31; 95% CI, 0.15-0.64; P = .002) were independently associated with a decreased risk of hospitalization for COVID-19. Among vaccinated rituximab-treated individuals with MS, receiving any vaccination dose more than 6 months after the last rituximab infusion was associated with a reduced risk of COVID-19 hospitalization (aOR, 0.22; 95% CI, 0.10-0.49). Conclusions and Relevance: This cohort study's findings suggest that rituximab-treated people with MS should be strongly encouraged to receive mRNA SARS-CoV-2 vaccines and boosters more than 6 months after their last rituximab infusion whenever possible. The low absolute risk of hospitalization for COVID-19 among mRNA-vaccinated individuals with MS should not preclude use of rituximab, which has marked efficacy, cost, and convenience advantages over other DMTs.
Subject(s)
COVID-19 , Multiple Sclerosis , Humans , Female , Middle Aged , Male , COVID-19 Vaccines/therapeutic use , SARS-CoV-2 , Rituximab/therapeutic use , Cohort Studies , Multiple Sclerosis/drug therapy , Retrospective Studies , Vaccination , Blindness , HospitalizationABSTRACT
BACKGROUND: Coronavirus disease 2019 (COVID-19) affects different people in different ways. Most infected people develop mild to moderate illness and recover without hospitalization. This case report presents a patient who had difficulty eradicating the corona virus due to being treated with rituximab, which depletes B lymphocytes and therefore disables the production of neutralizing antibodies. The regen-COV-2 antibody cocktail consists of two monoclonal antibodies, casirivimab and imdevimab. This cocktail successfully helped the patient's immune system eradicate the virus without auto specific severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody production. In vitro studies confirm that eradication of the intact the virus. This case report emphases the importance of providing external antiviral antibodies regularly, like the regen-COV-2 antibody cocktail, as post- and even pre- SARS-CoV-2 infection prophylaxis in patients treated with rituximab.
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Rituximab/therapeutic use , Immunocompromised HostABSTRACT
Rituximab (RTX) is a very effective treatment for autoimmune rheumatic diseases (AIRD), but it increases infection risk and impairs vaccine responses. Herein we evaluated the antibody response of RTX-treated patients to the supplemental COVID-19 vaccine. After the supplemental dose, 53.1% of patients had detectable antibody titers. Only 36% of patients who did not mount an antibody response after the original vaccine series did have detectable antibodies after the supplemental dose (seroconversion). Patients with undetectable CD20+ cell levels did not seroconvert while hypogammaglobulinemia was associated with a 15-times decrease in the likelihood of seroconversion. Although we noted 11 COVID-19 infections after the supplemental dose, no patients who received monoclonal antibodies pre-exposure prophylaxis had COVID-19 afterwards. We propose that patients receiving RTX should continue to be prioritized for prophylaxis measures and that vaccination should be timed after B cell recovery wherever possible.
Subject(s)
Autoimmune Diseases , COVID-19 Drug Treatment , COVID-19 , Humans , Rituximab/therapeutic use , Seroconversion , COVID-19 Vaccines , COVID-19/prevention & control , SARS-CoV-2 , Vaccination , Antibodies, Viral/therapeutic useABSTRACT
BACKGROUND Diffuse large B cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma (NHL). While bone marrow (BM) involvement is common in lymphoma, primary bone marrow (PBM) DLBCL is extremely rare. We present a case of PBM DLBCL discovered in a patient with COVID-19. CASE REPORT An 80-year-old man presented with generalized abdominal pain, weight loss, fever, fatigue, anorexia, and watery diarrhea over a 3-month period. Physical examination was unremarkable. Laboratory workup revealed anemia, thrombocytopenia, and elevated inflammation markers. SARS-COV-2 PCR was positive, while blood cultures were negative. A rapid decline in the white blood cell count in the following days prompted a BM biopsy, confirming the diagnosis of PBM DLBCL. Computed tomography (CT) did not show thoracic or abdominal lymphadenopathy. The patient received packed red blood cell and platelet transfusions, granulocyte colony-stimulating factor (G-CSF) for pancytopenia, and empirical antibiotics for suspected infection. Due to active COVID-19 and advanced age, cytotoxic chemotherapy was delayed. Rituximab and prednisone were initiated on day 9, followed by an infusion reaction, which led to treatment discontinuation. He died 2 days later. CONCLUSIONS Diagnosing PBM malignancy is challenging, especially with coexisting infection. It is essential to suspect underlying BM malignancy in patients with clinical deterioration and worsening pancytopenia despite adequate treatment. The diagnosis of PBM DLBCL requires the absence of lymphadenopathy, and the presence of histologically confirmed DLBCL. Prompt management with combination chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) with/without hematopoietic stem cell transplant can improve the prognosis.
Subject(s)
COVID-19 , Lymphadenopathy , Lymphoma, Large B-Cell, Diffuse , Pancytopenia , Aged, 80 and over , Anti-Bacterial Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bone Marrow/pathology , COVID-19/complications , Cyclophosphamide/therapeutic use , Doxorubicin/therapeutic use , Granulocyte Colony-Stimulating Factor/therapeutic use , Humans , Lymphadenopathy/pathology , Lymphoma, Large B-Cell, Diffuse/complications , Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, Large B-Cell, Diffuse/therapy , Male , Pancytopenia/etiology , Prednisone/therapeutic use , Rituximab/therapeutic use , SARS-CoV-2 , Vincristine/therapeutic useABSTRACT
BACKGROUND: Currently, observations are accumulating indicating the negative effect of therapy with a number of biologic disease-modifying anti-rheumatic drugs (bDMARDs) drugs on the course of COVID-19. These facts determine the relevance of studying the factors of severe course and unfavorable outcome in immuno-inflammatory rheumatic diseases (IIRD) patients treated with bDMARDs in order to develop tactics for managing this category of patients in a pandemic. AIM: To evaluate the influence of clinical and demographic factors on the risk of development, severity of the course and clinical outcomes of a new coronavirus infection in patients suffering from IIRD and receiving therapy with genetically engineered biological drugs. MATERIALS AND METHODS: A retrospective analysis of the database of the register of patients with IIRD receiving bDMARDs in the Novosibirsk region was performed, which included 318 patients, 94 of whom had indications of having suffered viral infection/pneumonia for the period from 01.04.2020 to 31.12.2020. RESULTS: According to the data obtained, at the time of the analysis, 94 people out of 318 patients with IIRD had a new coronavirus infection. Most (53%) of the patients had a mild infection. At the same time, the nosological form, the use of anti-rheumatic drugs and glucocorticoids did not increase the risks of severe coronavirus infection. When using bDMARDs, only anti-B-cell therapy (rituximab) associated with statistically significant increase in the risk of severe/extremely severe COVID-19. The mortality rate according to the analysis of the register was 6,38%. CONCLUSION: Patients with IIRD have a high risk of severe coronavirus infection, while the severity of the disease is associated with the type of therapy performed.
Subject(s)
Antirheumatic Agents , Biological Products , COVID-19 Drug Treatment , Pneumonia, Viral , Rheumatic Diseases , Humans , Rheumatic Diseases/drug therapy , Rheumatic Diseases/epidemiology , Retrospective Studies , Rituximab/therapeutic use , Pneumonia, Viral/chemically induced , Pneumonia, Viral/complications , Pneumonia, Viral/drug therapy , Antirheumatic Agents/adverse effects , Biological Products/adverse effectsABSTRACT
Progress has been made in COVID-19 vaccine development, with encouraging safety and efficacy data. The purpose of this study was to investigate the immunogenicity of inactivated COVID-19 vaccine in patients with autoimmune inflammatory rheumatic diseases (AIIRD). Patients with AIIRD (n = 101) were included in this study. All patients received 2 doses of inactivated COVID-19 vaccine. Serum anti-S1/RBD protein IgG was detected 2-16 weeks after the second vaccination. Seropositivity was defined as IgG ≥ 1.00 bound antibody unit S/CO. Immunogenicity of inactivated COVID-19 vaccine was assessed by seropositivity rate and the levels of serum IgG antibody against anti-S1/RBD protein, compared with the general population (n = 46). There was no difference by statistical significance in the seropositivity rate between patients with AIIRD (82.2%) and SLE (86.1%) and the control group (93.5%), p > 0.05. The level of anti-S1/RBD protein IgG antibodies in patients with AIIRD (median [IQR], 8.8 [2.2-17.3]) and SLE (median [IQR], 9.6 [2.4-20.4]) was comparable to that in the control group (median [IQR], 7.2 [3.1-14.2]), p > 0.05. Patients treated with glucocorticoids(GCs) (median dose, [IQR]: 2.5 mg/day [IQR 2.5-5.0]) or hydroxychloroquine(HCQ) or GCs + HCQ without other immunomodulatory medications, had an appropriate immunogenic response(88.1%) with high levels of anti-S1/RBD protein IgG(median [IQR], 12.1 [6.5-20.4]). Neither of patients treated with rituximab had positive serum antibodies, which was statistically significant, compared with the control group (p < 0.01). Compared with the control group, methotrexate(MTX) and iguratimod(IGU) was significantly reduced the level of anti-S1/RBD protein IgG antibodies. Inactivated COVID-19 vaccine had appropriate immunogenicity in patients with AIIRD. Immunogenicity of inactivated COVID-19 vaccine was severely impaired by rituximab, and also suppressed by MTX and IGU, while low doses of GC and HCQ had negligible effect.
Subject(s)
Autoimmune Diseases , COVID-19 , Lupus Erythematosus, Systemic , Rheumatic Diseases , Rheumatic Fever , Humans , COVID-19 Vaccines , Rheumatic Diseases/drug therapy , Rheumatic Diseases/epidemiology , Hydroxychloroquine/therapeutic use , Methotrexate/therapeutic use , Rituximab/therapeutic use , Autoimmune Diseases/epidemiology , COVID-19/prevention & control , Immunoglobulin G/therapeutic use , Antibodies, Viral/therapeutic use , Immunogenicity, VaccineABSTRACT
The helminth infection caused by Strongyloides stercoralis is widespread in tropical regions, but rare in European countries. Unfamiliarity with the disease and diagnostic obstacles could contribute to its lethal outcome. Frequent use of corticosteroids during the COVID-19 pandemic could increase its significance. The aim of this retrospective descriptive study was to explore disease patterns and discuss clinical dilemmas in patients with S. stercoralis hyperinfection treated at the University Hospital for Infectious Diseases 'Dr. Fran Mihaljevic' in Zagreb, Croatia, between 2010 and 2021. Five out of 22 (22.7%) immunosuppressed patients treated due to strongyloidiasis developed hyperinfection. All patients were male, median 64 years; four were immunosuppressed by corticosteroids (although ileum resection could have been the trigger in one) and one by rituximab. The diagnosis was established after a median of 1.5 months of symptom duration, accidentally in all patients, by visualizing the parasite in the gastric/duodenal mucosa in four cases, and bronchial aspirate in one. All patients were cachectic, four out of five had severe hypoalbuminemia and all suffered secondary bacterial/fungal infection. Despite combined antibiotic, antifungal and antihelmintic therapy, three out of five of the patients died, after failing to clear living parasites from stool samples. We can conclude that significant delays in diagnosis and lack of clinical suspicion were observed among our patients with the most severe clinical presentations of strongyloidiasis. Although being beyond diagnostic recommendations for strongyloidiasis, an early upper gastrointestinal endoscopy with mucosal sample analysis could expedite diagnosis in severe, immunosuppressed patients. The persistence of viable parasites in the stool despite antihelmintic therapy should be further investigated.
Subject(s)
Anthelmintics , COVID-19 , Strongyloides stercoralis , Strongyloidiasis , Humans , Male , Animals , Female , Strongyloidiasis/diagnosis , Strongyloidiasis/drug therapy , Strongyloidiasis/epidemiology , Retrospective Studies , Antifungal Agents/therapeutic use , Rituximab/therapeutic use , Pandemics , Anthelmintics/therapeutic use , Anti-Bacterial Agents/therapeutic useABSTRACT
Since the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak and COVID-19 vaccination, new-onset and relapsed clinical cases of membranous nephropathy (MN) have been reported. However, their clinical characteristics and pathogenesis remained unclear. In this article, we collected five cases of MN associated with SARS-CoV-2 infection and 37 related to COVID-19 vaccination. Of these five cases, four (4/5, 80%) had acute kidney injury (AKI) at disease onset. Phospholipase A2 receptor (PLA2R) in kidney tissue was negative in three (3/5, 60%) patients, and no deposition of virus particles was measured among all patients. Conventional immunosuppressive drugs could induce disease remission. The underlying pathogenesis included the subepithelial deposition of viral antigens and aberrant immune response. New-onset and relapsed MN after COVID-19 vaccination generally occurred within two weeks after the second dose of vaccine. Almost 27% of patients (10/37) suffered from AKI. In total, 11 of 14 cases showed positive for PLA2R, and 20 of 26 (76.9%) presented with an elevated serum phospholipase A2 receptor antibody (PLA2R-Ab), in which 8 cases exceeded 50 RU/mL. Conventional immunosuppressive medications combined with rituximab were found more beneficial to disease remission for relapsed patients. In contrast, new-onset patients responded to conservative treatment. Overall, most patients (24/37, 64.9%) had a favorable prognosis. Cross immunity and enhanced immune response might contribute to explaining the mechanisms of MN post COVID-19 vaccination.