RTX-treated Patients Research Articles

Real-life use of the PEXIVAS reduced-dose glucocorticoid regimen in granulomatosis with polyangiitis and microscopic polyangiitis

BackgroundThe PEXIVAS (Plasma exchange and glucocorticoids in severe antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis) trial showed that a reduced-dose glucocorticoid regimen (redGC) was non-inferior to a standard-dose regimen (standGC) with respect...

Defects in B-lymphopoiesis and B-cell maturation underlie prolonged B-cell depletion in ANCA-associated vasculitis

ObjectivesB-cell depletion time after rituximab (RTX) treatment is prolonged in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) compared with other autoimmune diseases. We investigated central and peripheral B-cell development to identify...

Hypogammaglobulinemia and Infection Events in Patients with Autoimmune Diseases Treated with Rituximab: 10 Years Real-Life Experience.

To investigate predictors of hypogammaglobulinemia (HGG) and severe infection event (SIE) in patients with autoimmune disease (AID) receiving rituximab (RTX) therapy. This was a retrospective study conducted in a tertiary medical center in China. Predictors of HGG or SIE were assessed using Cox analysis. Restricted cubic spline (RCS) analysis was applied to examine the correlation between glucocorticoid (GC) maintenance dose and SIE. A total of 219 patients were included in this study, with a cumulative follow-up time of 698.28 person-years. Within the study population, 117 patients were diagnosed with connective tissue disease, 75 patients presented with ANCA-associated vasculitis, and 27 patients exhibited IgG4-related disease. HGG was reported in 63.3% of the patients, where an obvious decline in IgG and IgM was shown three months after RTX initiation. The rate of SIE was 7.2 per 100 person-years. An increase in the GC maintenance dose was an independent risk factor for both hypo-IgG (HR 1.07, 95% CI 1.02-1.12, p = 0.003) and SIE (HR 1.06, 95% CI 1.02-1.1, p = 0.004). Further RCS analysis identified 7.48mg/d prednisone as a safe threshold dose for patients who underwent RTX treatment to avoid a significantly increased risk for SIE. HGG was relatively common in RTX-treated AID patients. Patients with chronic lung disease or who were taking ≥ 7.5mg/d prednisone during RTX treatment were at increased risk for SIE and warrant attention from physicians.

Distinct pulmonary patterns in ANCA-associated vasculitides: insights from a retrospective single center cohort study.

ANCA-associated vasculitides (AAV) comprise granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis. All forms may involve different organ systems, yet kidney and lung involvement are common and fatal in many cases. Here, we aimed to determine the predictive value of pulmonary disease manifestation and individual CT findings in AAV patients. Available CT scans and clinical information on mortality, renal outcomes, occurrence of relapses and damage scores were analysed retrospectively from a tertiary rheumatology center in Germany. We included a total of 94 AAV patients (49 with GPA, 41 with MPA). Forty-four patients had lung involvement with available CT scans, 70.5% of which with GPA and 72.7% with renal involvement. Nodule formation and cavities were more frequent among GPA patients, whereas ground-glass opacities (GGO), ILD and pleural effusion were observed predominantly in MPA patients. Over a median follow-up of 37months, GPA patients had a slightly higher overall mortality, whereas end-stage kidney failure rates were significantly increased in MPA patients. Relapse frequencies were comparable between both entities. The presence of GGO and pleural effusion were associated with higher relapse rates, whereas nodules were negatively correlated with relapses. Notably, RTX-treated patients had less infections as compared to individuals under different therapies. Our data demonstrate the outstanding importance of characteristic CT patterns in AAV diagnosis assessment. Especially certain CTpatterns including GGO and pleura effusion may help to identify patients who are at higher risk for relapsing disease.

Effects of Various Concentrations of Pronase on Flow Cytometric Crossmatching Patients Treated With Rituximab and Donor HLA-Specific Antibodies.

Pronase pretreatment can reduce rituximab (RTX) interference by degrading CD20 in B-cell flow cytometry crossmatch (FCXM) testing. However, it may also reduce the assay sensitivity by degrading HLA molecules. We investigated the effects of various pronase concentrations on RTX interference and the analytical sensitivity of B-cell FCXM testing. Using 59 patient serum samples and 38 donor lymphocyte samples, we designed 97 recipient-donor pairs and divided them into three groups according to RTX use and the presence of weak-to-moderate donor HLA-specific antibody (DSA) reactions: RTX+/DSA-, RTX+/DSA+, and RTX-/DSA+. FCXM was performed after pretreating lymphocytes with six different pronase concentrations (0, 0.5, 1, 2, 3, and 4 mg/mL). With B-FCXM testing, false-positive results due to RTX in the RTX+/DSA- group markedly decreased with increasing pronase concentrations. The median channel shift values in the RTX+/DSA+ and RTX-/DSA+ groups did not significantly decrease when the pronase concentration was increased from 1 mg/mL to 2 or 3 mg/mL. All eight RTX+/DSA+ cases that were positive at 1 mg/mL pronase but negative at 2 or 3 mg/mL had mean fluorescence intensity (MFI) DSA values of less than 3,000 except for DQ5 (MFI: 5,226). With T-cell FCXM, false-positive results were observed in 2.9% of 315 FCXM tests with pronase pretreatment. Higher concentrations (2 or 3 mg/mL) of pronase effectively eliminated RTX interference but still carried a risk for false negativity for weak DSA reactions in B-cell FCXM. Higher pronase concentrations can be used as an auxiliary method to detect moderate-to-strong DSA reactions in RTX-treated patients.

COVID-19 Vaccination Before Initiating Rituximab Treatment Induces Strong Serological Response in Autoimmune Rheumatic Disease, Reducing Post-Pandemic Concerns About the Impact of Rituximab.

Rituximab (RTX)-treated patients exhibit suboptimal responses to COVID-19 vaccines. However, existing research primarily involves patients already receiving RTX when vaccines were introduced, failing to account for the current landscape where patients are vaccinated before initiating RTX. Our objective was to compare the serological response to COVID-19 vaccines in patients vaccinated before or after RTX initiation. We included 254 RTX-treated patients with autoimmune inflammatory rheumatic diseases (AIIRDs) and 113 blood donors (BDs) in a retrospective, observational cohort study. Patients were categorized based on the timing of RTX treatment relative to primary COVID-19 vaccination. Serological vaccine responses were assessed using three immunoassays, and logistic regression analysis was used to identify predictors of serological response. Patients vaccinated before initiating RTX treatment had significantly higher seroconversion rates of SARS-CoV-2 immunoglobulin G (87%) and neutralizing antibodies (91%) compared with those receiving RTX before and after vaccination (n = 132) (61% and 65%, respectively). In the logistic regression analysis, a positive serological response was associated with the number of vaccines administered >9 months after the last RTX treatment. Patients receiving the highest number of vaccines with >9 months after RTX showed a response comparable to that of the BDs. Vaccinating before RTX initiation yields a robust serological response in patients with AIIRDs. Furthermore, we highlight the reversibility of antibody impairment after RTX treatment cessation, provided that adequate vaccinations occur within a minimum of 9 months after RTX. Our findings offer essential insights for clinical decision-making regarding COVID-19 vaccination and RTX treatment, alleviating concerns about future RTX use.

Trimethoprim-sulfamethoxazole prophylaxis during treatment of granulomatosis with polyangiitis with rituximab in the United States of America: a retrospective cohort study

BackgroundAntibiotic prophylaxis is recommended during ANCA-associated vasculitis (AAV) induction. We aimed to describe the frequency, persistence, and factors associated with trimethoprim-sulfamethoxazole (TMP-SMX) use in an adult population sample with granulomatosis with polyangiitis (GPA) treated with rituximab (RTX).MethodsWe identified adults with GPA treated with RTX within the Merative™ Marketscan® Research Databases (2011–2020). TMP-SMX prophylaxis was defined as a ge 28-day prescription dispensed within a month of starting RTX. We estimated TMP-SMX persistence, allowing prescription refill gaps of 30 days. Multivariable logistic regression and Cox proportional hazards regression assessed the factors associated with baseline TMP-SMX use and persistence, respectively. Covariates included age, sex, calendar year, insurance type, immunosuppressant use, hospitalization, and co-morbidities.ResultsAmong 1877 RTX-treated GPA patients, the mean age was 50.9, and 54% were female. A minority (n = 426, 23%) received TMP-SMX with a median persistence of 141 (IQR 83–248) days. In multivariable analyses, prophylaxis was associated with prednisone use in the month prior to RTX (ge 20 mg/day vs none, OR 3.96; 95% CI 3.0–5.2; 1–19 mg/day vs none, OR 2.63; 95% CI 1.8–3.8), and methotrexate use (OR 1.48, 95% CI 1.04–2.1), intensive care (OR 1.95; 95% CI 1.4–2.7), and non-intensive care hospitalization (OR 1.56; 95% CI 1.2–2.1) in the 6 months prior to RTX. Female sex (OR 0.63; 95% CI 0.5–0.8) was negatively associated with TMP-SMX use.ConclusionsTMP-SMX was dispensed to a minority of RTX-treated GPA patients, more often to those on glucocorticoids and with recent hospitalization. Further research is needed to determine the optimal use and duration of TMP-SMX prophylaxis following RTX in AAV.

Immune response to SARS-CoV-2 mRNA vaccination in multiple sclerosis patients after rituximab treatment interruption.

Peripheral B cell depletion via anti-CD20 treatment is a highly effective disease-modifying treatment for reducing new relapses in multiple sclerosis (MS) patients. A drawback of rituximab (RTX) and other anti-CD20 antibodies is a poor immune response to vaccination. While this can be mitigated by treatment interruption of at least six months prior to vaccination, the timing to resume treatment while maintaining subsequent vaccine responses remains undetermined. Here, we characterized SARS-CoV-2 S-directed antibody and B cell responses throughout three BNT162b2 mRNA vaccine doses in RTX-treated MS patients, with the first two doses given during treatment interruption. We examined B-cell mediated immune responses in blood samples from patients with RTX-treated MS throughout three BNT162b2 vaccine doses, compared to an age- and sex-matched healthy control group. The first vaccine dose was given 1.3 years (median) after the last RTX infusion, the second dose one month after the first, and the third dose four weeks after treatment re-initiation. We analyzed SARS-CoV-2 S-directed antibody levels using enzyme-linked immunosorbent assay (ELISA), and the neutralization capacity of patient serum against SARS-CoV-2 S-pseudotyped lentivirus using luciferase reporter assay. In addition, we assessed switched memory (CD19+CD20+CD27+IgD-), unswitched memory (CD19+CD20+CD27+IgD+), naïve (CD19+CD20+CD27-IgD+), and double negative (DN, CD19+CD20+CD27-IgD-) B cell frequencies, as well as their SARS-CoV-2 S-specific (CoV+) and Decay Accelerating Factor-negative (DAF-) subpopulations, using flow cytometry. After two vaccine doses, S-binding antibody levels and neutralization capacity in SARS-CoV-2-naïve MS patients were comparable to vaccinated healthy controls, albeit with greater variation. Higher antibody response levels and CoV+-DN B cell frequencies after the second vaccine dose were predictive of a boost effect after the third dose, even after re-initiation of rituximab treatment. MS patients also exhibited lower frequencies of DAF- memory B cells, a suggested proxy for germinal centre activity, than control individuals. S-binding antibody levels in RTX-treated MS patients after two vaccine doses could help determine which individuals would need to move up their next vaccine booster dose or postpone their next RTX infusion. Our findings also offer first indications on the potential importance of antigenic stimulation of DN B cells and long-term impairment of germinal centre activity in rituximab-treated MS patients.

Outcomes of remission induction therapy for ANCA-associated vasculitis in the elderly.

Treatment regimens combining glucocorticoids with cyclophosphamide or rituximab or both are used to induce remission in ANCA-associated glomerulonephritis (ANCA-GN). There is a paucity of data on the efficacy and safety of these regimens in elderly patients with ANCA-GN. This study aimed to examine outcomes and adverse events in elderly AAV patients with three induction regimens: cyclophosphamide (CYC), cyclophosphamide and rituximab (CYC + RTX), and rituximab (RTX). This single-center retrospective cohort study included patients 60years and older diagnosed with ANCA-GN. Baseline characteristics and outcomes across several clinical parameters were recorded and compared for significance using Kruskal-Wallis test, Chi-squared test, Fisher exact test, univariate, and multivariate logistic regression as appropriate. Cox proportional hazard regression model was used for survival analysis. Seventy-five patients were included. The mean (SD) age at diagnosis was 70 (± 6) years. The mean (SD) follow-up duration was 5.17 (± 3.47) years. Remission induction therapy with glucocorticoids plus CYC was used in 25 patients, glucocorticoids plus CYC and RTX in 12 patients, and glucocorticoids plus RTX in 38 patients. RTX-treated patients had a higher baseline estimated glomerular filtration ratio (eGFR) (p = 0.00009). High remission rates were achieved in all groups (100% vs. 100% vs. 94.6% respectively, p = 0.368). The incidence of end-stage renal disease (ESRD) at one year was 8% among all groups (p = 0.999). There was no difference in the number of infections requiring hospitalization (p = 0.822), but a statistical difference in leukopenia was noted (32% vs. 25% vs. 3% respectively, p = 0.005). The use of RTX only was associated with reduced leukopenia (aOR = 0.1, 95% CI = 0.005-0.8) after adjusting for other variables. CYC, CYC + RTX, and RTX are equally effective for remission induction in elderly patients with ANCA-GN. Induction therapy with RTX only was associated with a lower risk of leukopenia compared to CYC-containing regimens. Infections requiring hospitalization were similar among all groups. End-stage kidney disease at one year was comparable among the 3 groups. Key Points • Cyclophosphamide, Rituximab, and Cyclophosphamide+Rituximab are equally effective in remission induction in elderly patients with ANCA glomerulonephritis. • The use of Rituximab only was associated with a lower risk of bone marrow suppression compared to Cyclophosphamide only. • More information is needed on the comparative safety of induction therapy strategies in elderly ANCA glomerulonephritis patients.

Efficacy and safety of low-dose rituximab as induction therapy for antineutrophil cytoplasmic antibody-associated vasculitis with renal involvement: a Chinese case series

BackgroundRituximab (RTX) is a standard therapy for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). However, the most frequently used dose may lead to severe adverse effects (SAEs). We explored the efficacy and safety of low-dose RTX in Chinese patients with AAV.MethodsA total of 22 Chinese patients diagnosed with AAV with renal involvement, including 8 treated with low-dose RTX (400 mg of RTX total over 4 weeks) and 14 treated with cyclophosphamide (CYC), were evaluated. The baseline clinical and pathological data and laboratory parameters during follow-up at months 1, 3, 6, and 12 were collected retrospectively.ResultsThe baseline data showed no significant differences between the two groups. The median peripheral CD19+ cell counts in the RTX group decreased from 315.0/μL to 1.5/μL at 2 weeks, and to 2.5/μL at 1 month after the first dose. The median SCr level decreased from 267.8 μmol/L before treatment to 151.45 μmol/L at 1 month, 132.75 μmol/L at 3 months, 123.2 μmol/L at 6 months, and 151.9 μmol/L at 12 months in RTX-treated patients. The improvements in renal function, proteinuria, and ANCA titre were not significantly different between the two groups. The SAE rate was significantly lower in the RTX group (one SAE of pneumonia) compared with the CYC group.ConclusionsThis is the first report that low-dose RTX could be effective for the treatment of Chinese patients with AAV with renal involvement.

SARS-CoV-2 Vaccination Effectiveness in Rituximab-Treated Patients Affected by Pemphigus Vulgaris

SARS-CoV-2 Vaccination Effectiveness in Rituximab-Treated Patients Affected by Pemphigus Vulgaris

Rituximab in myositis: where are we now? A survey of current usage.

Dear Editor, In a retrospective analysis 7 years ago, it was estimated that ∼78% of patients with inflammatory myositis were considered to have improved with rituximab (RTX) [1]. The International Myositis Assessment & Clinical Studies (IMACS) group felt it was timely to undertake a prospective study of the use of RTX in myositis. Members of the group were invited to send information about RTX-treated patients from July 2021 during the following year. After lengthy discussions, a simple proforma was produced and sent to the IMACS members on four occasions during the year. The key aims of the study were to: assess the current use of B cell depletion in patients with myositis; obtain background information about which particular patients are being treated in this way; and ascertain if B cell depletion continues to be effective in myositis. Fifty myositis patients from nine referring centres were distinguished in two groups based on the time of first RTX infusion (29 had been prescribed it before July 2021, designated previous users, and 21 were new starters). The patients’ demographic features, characteristics of myositis and treatment response are summarized in Table 1. The median time from the diagnosis until the first RTX infusion was 21.5 months (interquartile range = 65). Most were females (74%), of Caucasian origin (56%) and had a diagnosis of anti-synthetase syndrome (56%). Three out of 50 patients were myositis-specific antibody (MSA) negative. The most common immunosuppressive agent used with RTX was CS (84%), followed by MMF (36%), MTX (10%), AZA (8%), CSA (8%) and CYC (2%). RTX was preferred as a first line drug with steroids in five patients (two were reported to have responded well). Effectiveness was assessed by the treating physician on the basis of clinical observation, reduction in the creatine kinase and capacity to reduce steroids. Based on these components, RTX was reported to be effective in 43 patients (86%), and no benefit was seen in 7 patients (14%). Treatment response was found to be similar in both groups (89.7% vs 81%, P = 0.434). Of note, no statistically significant difference was seen in RTX effectiveness among types of myositis (anti-synthetase syndrome vs others), MSAs and genders. Steroid taper was successfully achieved in 78.7% of patients. Adverse events were noted in seven patients; all were infectious complications with requirement for hospitalization in three cases. Three minor side effects including two infusion reactions and one nausea were reported during the entire follow-up.

Rituximab-treated rheumatic patients: B cells predict seroconversion after COVID-19 boost or revaccination in initial vaccine non-responders.

To investigate the effect of either a booster vaccine (one dose) or revaccination (two doses 3 weeks apart) on the antibody response to the COVID-19 mRNA vaccines in patients with rheumatic disease (RD) treated with rituximab (RTX) who had not produced vaccine-reactive antibodies after the initial two vaccine doses. Further, to examine if B cell levels in peripheral blood predicted seroconversion. We included 91 RTX-treated RD patients previously vaccinated against COVID-19. Patients were offered revaccination or a single booster vaccination with an mRNA vaccine. Serum total antibodies against SARS-CoV-2 spike protein were measured before and 6 weeks after the last vaccine dose. B cells (CD19+CD45+) were measured by flow cytometry at inclusion. Of RD patients with undetectable SARS-CoV-2 antibody levels before inclusion, seroconversion was seen in 38% 6 weeks after the booster dose and 32% after revaccination. Patients receiving revaccination had significantly higher antibody levels than patients receiving a booster dose (P < 0.001). In both univariate and multivariate logistic regression analysis, only B cells higher than 10/µl before boost or revaccination were associated with seroconversion (P = 0.009 and P = 0.01, respectively). Seroconversion was independent of age, gender, diagnosis, cumulative RTX dose, RTX treatment time and time since last RTX treatment. Continuously impaired humoral response to mRNA vaccines was found in most RTX-treated patients after a booster dose or revaccination. Seroconversion was observed in approximately one-third of the patients. Measurable B cells before boosting or revaccination was the strongest predictor of antibody response after boost or revaccination.

Applicability of glucocorticoid toxicity index in pemphigus: Comparison between two groups of rituximab-treated and rituximab-naïve patients.

Rituximab (RTX) combined with short-term glucocorticoids (GC) is an effective therapeutic option for pemphigus. The newly developed Glucocorticoid Toxicity Index (GTI) tool provides the possibility to measure GC toxicities over time. To compare 1-year GTI between two groups of RTX-treated and RTX-naïve patients with pemphigus. The responsiveness of the GTI was also investigated. A prospective cohort of 129 adults with newly diagnosed pemphigus was conducted. GC-related toxicities were assessed at 3-month intervals according to Composite and Specific lists of the GTI. Of the patients, 76.7% (n= 99) received RTX. Throughout the time intervals, RTX-treated patients had lower GTI compared to RTX-naïve ones (p= 0.036). The mean GTI at 1-year was 34.3 in the RTX-treated group and 50.8 in the RTX-naïve group (p= 0.04). The most commonly observed GC-related toxicity was neuropsychiatric manifestations for 34% (224 events). The relapse rate of RTX-treated patients (1%) was significantly lower than RTX-naïve patients (10%) (p= 0.037). The GTI showed no correlation with cumulative GC consumption in both groups (p> 0.05, both). Patients treated with GC alone had remarkably higher GTI than patients treated with GC plus RTX. The GTI is an applicable tool to quantitatively capture GC toxicities at the patient level in pemphigus.

Seroconversion among rituximab-treated patients following SARS-CoV-2 vaccine supplemental dose

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.

P245 Identifying predictors of short-term response to rituximab in extra-glandular primary Sjogren’s Syndrome

Abstract Background/Aims Randomised controlled trials (RCTs) of rituximab (RTX) in primary Sjogren’s syndrome (pSS) have failed to alleviate glandular symptoms and fatigue. The question remains as to whether B-cell depleting therapies have a place for the treatment of pSS. Post-hoc analyses from RCTs showed greater improvement in objective measures such as salivary flow rate, salivary gland ultrasound and histology scores in RTX-treated group vs placebo. Moreover, there are limited data on efficacy of the initial and repeat cycles of RTX on extra-glandular pSS. Here, our objectives were to assess the effectiveness of RTX on extra-glandular symptoms and identify predictors of short-term response with a view to personalised B-cell depleting therapy in pSS. Methods A retrospective longitudinal cohort study was conducted in 40 consecutive RTX-treated pSS patients in a single-centre for over 15 years. All patients fulfilled the 2002 AEG criteria and were CCP negative. Clinical response at 6 months was defined as ≥ 3 point reduction of ESSDAI from baseline. B-cell subsets were measured using highly sensitive flow cytometry. Predictors of short-term response were analysed using penalised logistic regression. Results 38/40 (95%) patients were female, mean (SD) age 54 (13.7) years, median (IQR) disease duration 5 (2-9) years, 39/40 (98%) had positive ANA and 28/40 (70%) were on concomitant immunosuppressant (IS). Mean (SD) ESSDAI at RTX initiation was 11.5 (6.7) and main domains for RTX were articular (73%), skin (23%), haematological (18%), PNS (15%) and lungs (10%). 169 RTX cycles were administered with a total follow-up of 165PY. In Cycle 1 (C1) RTX, the proportion of patient achieving ESSDAI response from baseline was 29/40 (73%; 95% CI 58-87). There were significant reductions in ESSDAI, daily prednisolone dose and IgG levels at 6 months (all p &amp;lt; 0.05). Of C1 responders, 23/29 received retreatment on clinical relapse; of which 8/23 (35%) lost response [secondary non-depletion non-response (2NDNR) associated with anti-RTX antibodies as we previously observed in SLE=4 (17%)]; side effects=1; ineffective=3. Of C1 non-responders, 9/11 were retreated but only 2/9 responded in C2. Overall, 13/40 (33%) discontinued RTX within two cycles. In multivariable analysis, concomitant immunosuppressant [OR 0.07 (95% CI 0.01-0.52); p = 0.010] and achieving compete B-cell depletion in C1 [0.04 (0.02-0.82); 0.036] reduced non-response to RTX. Conclusion All patients with pSS should be co-prescribed immunosuppressant with RTX and future therapeutics should aim to achieve complete depletion. About one in six pSS patients lose response in repeat cycles which is associated with 2NDNR phenomenon. The use of humanised or next-generation type 2 anti-CD20 antibodies should overcome these issues and improve the clinical response of extra-glandular pSS. Disclosure S. Pepple: None. J. Arnold: None. E. M Vital: Consultancies; Dr Vital has received consulting fees from Roche. Grants/research support; Dr Vital has received funding for research from Roche. A. C Rawstron: None. C. Pease: None. S. Dass: None. P. Emery: Consultancies; Prof Emery has received consulting fees from Roche. Grants/research support; Prof Emery has received funding for research from Roche. M. Md Yusof: None.

Comparison of follicular T helper cells, monocytes, and T cells priming between newly diagnosed and rituximab-treated MS patients and healthy controls.

Background and purpose:The use of anti-CD20 monoclonal antibodies like rituximab (RTX) to deplete B cells has practical therapeutic implications in multiple sclerosis (MS) patients. However, the therapy’s impact on other immune cells is also important. Therefore, in this study, we assessed the effects of RTX therapy on Tfh cells, T cells, T cells priming, and monocytes in MS patients compared to newly-diagnosed MS patients and healthy subjects.Experimental approach:Thirty newly-diagnosed and RTX-treated MS patients and healthy control were included. Peripheral blood mononuclear cells were isolated from whole blood for assessment of Tfh cells, CD4+, CD8+, CD4+CD45RA+, CD3+HLA-DR+, and CD3+CD4+CD25+ T cells by flow cytometry. Whole blood was lysed by lysis solution to assess CD45+CD14+ monocytes by flow cytometry. Also, the serum level of interleukin 21 was measured by the ELISA method.Findings / Results:We showed that RTX treatment led to a decrease in Tfh cells and their predominant cytokine, interleukin 21. Also, we found a statistically significant reduction in CD3+HLA-DR+ and CD3+CD4+CD25+ T cells in RTX-treated patients compared to new cases and healthy control. Moreover, we found a decrease in the CD45+ CD14+ monocyte population in the RTX-treated group compared to the healthy control.Conclusion and implications:Our data suggest that following treatment with RTX, Tfh cells, monocytes, and T cells priming declined happened, and fewer T cells were activated. Also, due to the interaction between B cells and Tfh cells, Tfh targeting could be assessed as a therapeutic strategy in MS.

Efficacy and safety of SARS-CoV-2 revaccination in non-responders with immune-mediated inflammatory disease

ObjectivesTo test whether patients with immune-mediated inflammatory disease (IMIDs), who did not respond to two doses of the SARS-CoV-2 vaccine, develop protective immunity, if a third vaccine dose is administered.MethodsPatients...

Effective Rituximab Treatment in Patients with Neuromyelitis Optica Spectrum Disorders Compared with Azathioprine and Mycophenolate.

IntroductionAs an autoimmune central nervous system disease characterized by inflammation and demyelination, neuromyelitis optica (NMO) has been extensively investigated. A specific antigenic target, astrocytic water channel aquaporin-4 (AQP4) has already been identified, and it can be recognized explicitly by the autoantibody marker NMO-IgG. Along with the immune attacks, clinical disabilities would gradually accumulate. As there has been no validated and well-recognized therapy for NMO till now, preventing and postponing attack using immunosuppressive therapies is the primary treatment option.MethodsIn the current retrospective study, the effect of immunosuppressive agents was investigated through a long-term follow-up. To assess the long-term effectiveness and safety of rituximab (RTX), azathioprine (AZA), and mycophenolate mofetil (MMF) therapies, all 129 patients with NMO spectrum disorders (NMOSD) who received at least one of these treatments were studied, including 55 seropositive for AQP4-Ab and 74 seronegative for AQP4-Ab.ResultsThe median post-treatment annualized relapse rate (ARR) was lower than the pre-treatment rates in all AQP4+Ab groups (from 1.0 to 0.7 in RTX, from 0.8 to 0.3 in AZA, and from 0.85 to 0.35 in MMF). Meanwhile, the ARR also decreased in all AQP4−Ab groups (from 0.3 to 0.2 in RTX, from 0.9 to 0.5 in AZA, and from 0.9 to 0.4 in MMF). Disability condition improved in the Expanded Disability Status Scale (EDSS) in all AQP4+Ab groups (from 4.0 to 2.75 in RTX, from 3.5 to 2.5 in AZA, and from 3.0 to 2.0 in MMF) and in all AQP4−Ab groups (from 3.0 to 2.5 in RTX, from 3.0 to 2.5 in AZA, and from 3.5 to 2.0 in MMF). There was no statistically significant difference between the post-treatment and pre-treatment changes of EDSS and ARR in the RTX, AZA, and MMF groups (P > 0.05). However, according to Kaplan–Meier survival analysis, RTX-treated patients were more likely to be relapse-free after long-term follow-up than those who received AZA or MMF therapy. Meanwhile, adverse effects were noted in three out of 23 patients with RTX treatment, five of 32 with AZA treatment, and three of 21 with MMF treatment. No serious adverse events were observed in all treatment groups during the study.ConclusionsRTX, AZA, and MMF therapies efficiently lowered the relapse frequency and disability in both of the AQP4-Ab seropositive or seronegative patients with NMO. Furthermore, low dosage of RTX is recommended for the patients with NMO owing to its long-term effectiveness and safety.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40120-021-00298-5.

Risk factors of impaired humoral response to COVID-19 vaccination in rituximab-treated patients.

ObjectiveTo identify which factors influence humoral response to coronavirus disease 2019 (COVID-19) vaccination in rituximab (RTX)-treated patients.MethodsThis was an observational, prospective, usual care study including consecutive patients with inflammatory rheumatic diseases in maintenance therapy with RTX. All patients received a two-dose regimen COVID-19 vaccination. Serum IgG antibody levels against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike proteins were measured at the time of the new RTX infusion.ResultsFrom the recruited patients, 16/45 (36%) produced antibodies reaching the assay cut-off value of 15 AU/ml and 29/45 (64%) had a negative serology. Within RTX-treated patients, 25 (56%) had undetectable B cells. Negative serology was associated with undetectable B cells (24/25 vs 5/20, P < 0.001). Moreover, SARS-CoV-2 spike antibodies correlated with CD19 counts (r = 0.86, P < 0.001). The effect of RTX and MTX was additive in terms of seroconversion rates (23% vs 50% in patients receiving RTX in monotherapy, P = 0.12) and SARS-CoV-2 spike antibody levels [3.80 (95% CI 3.80, 7.50) vs 75 (95% CI 3.8, 353) AU/ml in patients receiving RTX in monotherapy; P = 0.025]. Multivariate analyses including demographics, disease characteristics, gammaglobulin levels, RTX and other therapies used, CD19 counts, and the time between the last RTX infusion and vaccination identified detectable B cells as the only variable independently associated with seropositivity [odds ratio 35.2 (95% CI 3.59, 344.20)].ConclusionsB cell depletion is the main independent contributing factor of antibody response to SARS-CoV-2 vaccination in RTX-treated patients. Monitoring CD19 may be of interest to identify the most appropriate period to perform vaccination.