Efficacy Of Rituximab In Patients Research Articles

A Comparative Analysis of Efficacy of Rituximab in Patients with Primary Membranous Nephropathy

A Comparative Analysis of Efficacy of Rituximab in Patients with Primary Membranous Nephropathy

Efficacy of rituximab in the treatment of epidermolysis bullosa acquisita.

Epidermolysis bullosa acquisita (EBA) is a chronic mucocutaneous disease that is mediated by antibodies that bind collagen VII. The treatment of EBA can be challenging and often multiple immunomodulatory drugs are required. Rituximab has been reported to be an effective treatment for recalcitrant EBA, although its evidence base is limited to case reports and case series. This study therefore aimed to evaluate the efficacy of rituximab in patients with EBA. EBA patients treated with rituximab were identified by searching electronic medical records. Diagnostic criteria for EBA were as follows; mechanobullous skin lesions and / or mucosal ulceration, indirect immunofluorescence localising to the base of salt split skin and positive collagen VII antibodies. Clinical disease activity, collagen VII antibody levels and serum immunoglobulins were recorded at each follow up visit over 600 day period. Treatment responses were classified as follows; complete remission (CR) as the absence of new or established lesions on minimal therapy for 2 months, partial remission (PR) as transient lesions that heal within 1 week on minimal therapy and active disease (AD) as the development of new lesions. 14 patients with EBA were treated with rituximab. CR or PR was observed in 11 patients, and the duration of response varied between 4 and 24 months. A reduction in collagen VII antibody levels was observed in all patients. No significant adverse events were reported. Rituximab is a safe and effective treatment for patients with recalcitrant EBA although there was significant heterogeneity in the disease response.

The emergence of circulating activated autoreactive desmoglein 3-specific follicular regulatory T cells is associated with long-term efficacy of rituximab in patients with pemphigus vulgaris.

Pemphigus vulgaris (PV) is characterized by autoantibodies targeting keratinocyte adhesion proteins desmoglein (Dsg) 1 and 3, and by the human leukocyte antigen (HLA) predisposition allele HLA-DRB1*0402. Treatment using rituximab (RTX) combined with short-term corticosteroids (CS) allows disease control and long-lasting remission. The principal aim of this study was to evaluate the impact of RTX on the circulating subpopulations of Dsg3-specific T lymphocytes that specifically regulate B-cell responses: follicular helper T (Tfh) and follicular regulatory T (Tfr) lymphocytes. Using the HLA-DRB1*0402 tetramer loaded with the Dsg3 immunodominant peptide, we used flow cytometry to analyse the frequency, polarization and activation status of blood Dsg3-specific follicular T-cell populations at baseline, month (M) 6 and long-term follow-up (M60-90) from patients with PV. At baseline, we observed a predominance of Tfh1* and Tfh17 subsets and an underrepresentation of the Tfh2 subset among autoreactive Dsg3-specific Tfh cells compared with nonautoreactive Tfh cells. RTX treatment induced a decrease of autoreactive Tfh cells with no effect on their polarization during follow-up. In parallel, we observed the emergence of a Dsg3-specific Tfr subpopulation with a significant overexpression of the surface activation markers PD1, ICOS and CD25 that was not observed at the surface of autoreactive Tfh and nonautoreactive Tfr cells of the same patients with PV. In contrast, very few Dsg3-specific Tfr cells were observed in patients with PV who were treated with CS alone. Here we show that the emergence of circulating autoreactive Dsg3-specific Tfr cells is associated with the long-term efficacy of RTX in patients with PV.

Rituximab in the Treatment of LRP4-Antibody-Positive Myasthenia Gravis: A Case Report

Antibodies against LRP4 were found in 2-4% of patients with myasthenia gravis (MG). LRP4-antibody-positive (LRP4+) MG presents with more severe disease with bulbar involvement. No standard treatment guideline has been established for this subtype. We identified a LRP4+MG patient with severe symptoms including bulbar dysfunction that were refractory to standard therapy. Rituximab was started due to treatment failure with standard therapy. At the time of initiation of rituximab, patient was on plasmapheresis every 1-2 weeks. Her work and quality of life were greatly compromised. Six weeks after initiating rituximab therapy, remarkable improvements in dyspnea, dysphagia, ptosis, and proximal limb muscle strength were reported without adverse events. Improvements in 3 standardized Myasthenia Gravis scoring systems were observed. The maintenance plasmapheresis was discontinued and pyridostigmine dose decreased by 50% because of sufficient symptom control. Stable improvement was achieved with rituximab maintenance therapy spaced 5 months apart. Our case demonstrates rapid onset of efficacy of rituximab in patient with refractory LRP4+MG. This response and the proposed mechanism of action of LPR4-Ab suggest that the efficacy of rituximab in LRP4+MG may parallel that in MuSK+MG. Further exploration of this treatment option is warranted.

Efficacy of rituximab for patients with anti-glomerular basement membrane disease.

Efficacy of rituximab for patients with anti-glomerular basement membrane disease.

Efficacy of rituximab in patients with rheumatoid arthritis.

To determine the efficacy of rituximab 2×500mg in rheumatoid arthritis patients. The descriptive case series was conducted at the Department of General Medicine, Lady Reading Hospital, Peshawar, Pakistan, from November 25, 2018, to May 24, 2019, and comprised patients of either gender aged 30-60 years with rheumatoid arthritis diagnosis for >6 months. The patients received 2 doses of rituximab 2×500mg through intravenous infusion with pre-medications as a standard protocol. A follow-up visit was recommended for each patient after 24 weeks. The efficacy of the treatment in terms of disease progression and improvement were observed using the Disease Activity Score-28 scale at the baseline and on follow-up. Data was analysed using SPSS 20. Of the 97 patients, 83(85.6%) were female and 14(14.4%) were male. The overall mean age was 50.68±14.27 years. The baseline score was 6.68±1.14 while the follow-up score was 4.62±0.93 (p<0.05). In terms of efficacy, 25(25.8%) patients showed no improvement, while 72(74.2%) had improvement. Rituximab 2×500mgI was found to be an effective treatment option for rheumatoid arthritis patients.

What does endemic COVID-19 mean for the future of rituximab?

What does endemic COVID-19 mean for the future of rituximab?

Rituximab Is Preferable to Cyclophosphamide for Treatment of Membranous Nephropathy: CON.

This is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the PRO: 10.34067/KID.0001842021 and the COMMENTARY: 10.34067/KID.0002492021

Efficacy of rituximab in patients with polymyalgia rheumatica: a double-blind, randomised, placebo-controlled, proof-of-concept trial

Background Glucocorticoids remain the cornerstone of polymyalgia rheumatica treatment, but their use has several drawbacks, such as long treatment duration and glucocorticoid-related adverse events. Effective glucocorticoid-sparing agents with a strong evidence base in polymyalgia rheumatica are absent. As B cells have been implicated in the pathogenesis of polymyalgia rheumatica, we aimed to evaluate the efficacy of rituximab for the treatment of polymyalgia rheumatica. Methods We did a double-blind, randomised, placebo-controlled, proof-of-concept trial at Sint Maartenskliniek, Nijmegen, Netherlands. We enrolled patients with polymyalgia rheumatica according to the 2012 European League Against Rheumatism and American College of Rheumatology criteria, who were recently diagnosed or who had relapsed on prednisolone and were unable to taper their dose to less than 7·5 mg per day. Participants were randomly assigned (1:1) to a single intravenous infusion of rituximab 1000 mg or placebo, with a 17-week glucocorticoid tapering scheme. Participants and care and research personnel were masked to treatment assignment and randomisation sequence. The primary outcome was glucocorticoid-free remission at 21 weeks after infusion in patients who completed the study. This trial is registered with EudraCT (2018-002641-11) and the Dutch trial database (NL7414). Findings Between Jan 14, 2019, and March 10, 2020, 116 patients were screened and 49 (42%) were enrolled. 47 patients (38 who were recently diagnosed, nine who had relapsed on prednisolone) completed the study: 23 (49%) in the rituximab group and 24 (51%) in the placebo group. Mean age (SD) in years was 64 (8) in the rituximab group and 66 (10) in the placebo group, the proportion of women was 11 (48%) of 23 versus 13 (54%) of 24, and all participants were White. 11 (48%) of 23 patients in the rituximab group and five (21%) of 24 in the placebo group achieved glucocorticoid-free remission at 21 weeks (difference 27% [one-sided 95% CI 4]; relative risk 2·3 [1·1]; p=0·049). Ten infusion-related complaints occurred in the rituximab group versus three in the placebo group (relative rate 3·5 [one-sided 95% CI 1·3]). One serious adverse event occurred (pulmonary embolism; in the rituximab group), and there were no deaths. Interpretation Rituximab was shown to be efficacious in combination with 17-week glucocorticoid treatment compared with glucocorticoid treatment alone in terms of glucocorticoid-free remission in patients with polymyalgia rheumatica. If these findings are confirmed by larger trials, rituximab could be a valuable glucocorticoid-sparing treatment for patients with polymyalgia rheumatica. Funding Sint Maartenskliniek. Glucocorticoids remain the cornerstone of polymyalgia rheumatica treatment, but their use has several drawbacks, such as long treatment duration and glucocorticoid-related adverse events. Effective glucocorticoid-sparing agents with a strong evidence base in polymyalgia rheumatica are absent. As B cells have been implicated in the pathogenesis of polymyalgia rheumatica, we aimed to evaluate the efficacy of rituximab for the treatment of polymyalgia rheumatica. We did a double-blind, randomised, placebo-controlled, proof-of-concept trial at Sint Maartenskliniek, Nijmegen, Netherlands. We enrolled patients with polymyalgia rheumatica according to the 2012 European League Against Rheumatism and American College of Rheumatology criteria, who were recently diagnosed or who had relapsed on prednisolone and were unable to taper their dose to less than 7·5 mg per day. Participants were randomly assigned (1:1) to a single intravenous infusion of rituximab 1000 mg or placebo, with a 17-week glucocorticoid tapering scheme. Participants and care and research personnel were masked to treatment assignment and randomisation sequence. The primary outcome was glucocorticoid-free remission at 21 weeks after infusion in patients who completed the study. This trial is registered with EudraCT (2018-002641-11) and the Dutch trial database (NL7414). Between Jan 14, 2019, and March 10, 2020, 116 patients were screened and 49 (42%) were enrolled. 47 patients (38 who were recently diagnosed, nine who had relapsed on prednisolone) completed the study: 23 (49%) in the rituximab group and 24 (51%) in the placebo group. Mean age (SD) in years was 64 (8) in the rituximab group and 66 (10) in the placebo group, the proportion of women was 11 (48%) of 23 versus 13 (54%) of 24, and all participants were White. 11 (48%) of 23 patients in the rituximab group and five (21%) of 24 in the placebo group achieved glucocorticoid-free remission at 21 weeks (difference 27% [one-sided 95% CI 4]; relative risk 2·3 [1·1]; p=0·049). Ten infusion-related complaints occurred in the rituximab group versus three in the placebo group (relative rate 3·5 [one-sided 95% CI 1·3]). One serious adverse event occurred (pulmonary embolism; in the rituximab group), and there were no deaths. Rituximab was shown to be efficacious in combination with 17-week glucocorticoid treatment compared with glucocorticoid treatment alone in terms of glucocorticoid-free remission in patients with polymyalgia rheumatica. If these findings are confirmed by larger trials, rituximab could be a valuable glucocorticoid-sparing treatment for patients with polymyalgia rheumatica.

Safety and efficacy of rituximab in patients with diffuse large B-cell lymphoma in Malawi: a prospective, single-arm, non-randomised phase 1/2 clinical trial

SummaryBackgroundThere are no clinical trials involving patients with diffuse large B-cell lymphoma (DLBCL) in sub-Saharan Africa since antiretroviral therapy (ART) for HIV became widely available in this region. We aimed to establish the safety and efficacy of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with DLBCL in Malawi.MethodsThis prospective, single-arm, non-randomised phase 1/2 clinical trial was done at Kamuzu Central Hospital Cancer Clinic (Lilongwe, Malawi). Eligible patients were adults (aged 18–60 years) with newly diagnosed DLBCL, an Eastern Cooperative Oncology Group performance status of 0–2, a CD4 count of 100 cells per μL or higher (if HIV-positive), measurable disease by physical examination, an absolute neutrophil count of 1000×109 cells per L or higher, a platelet count of 100×109 platelets per L or higher, a serum creatinine concentration of 132·60 μmol/L or less, a total bilirubin concentration of 34·21 μmol/L or less, a negative urine pregnancy test in women of childbearing potential, and no previous cytotoxic therapy. Pregnant or breastfeeding women, and individuals with CNS involvement from DLBCL, chronic hepatitis B infection (unless they were receiving tenofovir plus lamivudine), or any other comorbidities that would compromise the protocol objectives were excluded. Eligible patients received intravenous rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, and vincristine 1·4 mg/m2 (maximum 2 mg/m2), and oral prednisone 100 mg or an equivalent drug every 21 days for up to six cycles. HIV-positive patients received concurrent ART. The primary outcome was the proportion of patients with National Cancer Institute Common Terminology Criteria for Adverse Events grade 3 or 4 non-haematological toxic effects or treatment-related deaths after six cycles of treatment. Secondary efficacy outcomes included the proportion of patients with a complete response after six cycles of treatment, and progression-free survival and overall survival at 12 months and 24 months. This trial is registered with ClinicalTrials.gov, NCT02660710.FindingsBetween Aug 1, 2016, and July 31, 2019, 76 patients were screened, of whom 37 were eligible for the study and received R-CHOP. The median age of patients was 44 years (IQR 39–49) and 16 (43%) were women. Of all 37 patients, 20 (54%) had stage III or IV DLBCL, and the age-adjusted international prognostic index was 2 or higher in 25 (68%) patients. 27 (73%) patients were HIV-positive, with a median CD4 count of 208 cells per μL (IQR 144–422), and 21 (78%) patients were receiving ART at enrolment. Patients completed a median of six cycles (IQR 4–6). Grade 3 or 4 non-haematological toxic effects were reported in 12 (32% [95% CI 19–49]) patients, the most common of which was infection (nine [24%] patients). Of 16 (43%) deaths, ten were due to progression of DLBCL, four were due to treatment-related complications, and two were due to other causes, yielding a treatment-related mortality of 11% (95% CI 4–26%). Grade 3 or 4 neutropenia was observed in 26 (70%) patients, and grade 3 or 4 anaemia was observed in 11 (29%) patients. A total of 22 (59%) patients had a complete response. Overall survival was 68% (95% CI 50–80) at 12 months and 55% (37–70) at 24 months, and progression-free survival was 59% (42–73) at 12 months and 53% (35–68) at 24 months.InterpretationR-CHOP could be feasible, safe, and efficacious in patients with DLBCL in Malawi. This is the first completed clinical trial on DLBCL focused on sub-Saharan African populations. Given the paucity of data on treatment of DLBCL from this region, these results could inform emerging cancer treatment programmes in sub-Saharan Africa.FundingThe University of North Carolina Lineberger Comprehensive Cancer Center.

The efficacy of rituximab in patients with neuromyelitis optica spectrum disorder: A real-world study from Turkey.

Neuromyelitis optica spectrum disorders (NMOSD) are a group of antibody-mediated chronic inflammatory diseases of the central nervous system. Rituximab is a monoclonal antibody that leads to a reduction in disease activity. To evaluate the efficacy of rituximab as monotherapy in NMOSD and to determine whether the efficacy varies depending on the presence of antibodies in this cohort. This multicentre national retrospective study included patients with NMOSD treated with rituximab at least for 12months from Turkey. The primary outcomes were the change in the annualised relapse rate, the Expanded Disability Status Scale (EDSS), the number of relapse and radiological activity-free patients. A total of 85 patients with NMOSD were included in the study. Of 85 patients, 58 (68.2%) were seropositive for anti-Aquaporin4-IgG (antI-AQP4-IgG). All patients were Anti-Myelin Oligodendrocyte Glycoprotein IgG (anti-MOG-IgG) negative. The median follow-up for rituximab treatment was 21months (Q1 16-Q3 34.5). During rituximab treatment, the mean annualised relapse rate (ARR) significantly decreased from 1.45±1.53 to 0.15±0.34 (P<.001). In subgroup analyses, the mean ARR decreased from 1.61±1.65 to 0.20±0.39 in the seropositive group and 1.10±1.19 to 0.05±0.13 in the seronegative group. The mean EDSS improved from 3.98±2.04 (prior to treatment onset) to 2.71±1.59 (at follow-up) (P<.001). In the seropositive group, mean EDSS decreased from 3.94±1.98 to 2.67±1.54, and in the seronegative group, mean EDSS decreased from 4.07±2.21 to 2.79±1.73. There was no significant difference between anti-AQP4-IgG (+) and (-) groups in terms of ARR and EDSS. Sixty-four patients (75.2%) were relapse-free after the initiation of treatment. Seventy patients (82.3%) were radiological activity-free in the optic nerve, area postrema and brainstem. Additionally, 78 patients (91.7%) showed no spinal cord involvement after the treatment. Rituximab therapy is efficacious in the treatment of Turkish NMOSD patients independent of the presence of the anti-AQP4-IgG antibody.

All-case Japanese post-marketing surveillance of the real-world safety and efficacy of rituximab treatment in patients with refractory nephrotic syndrome

BackgroundRituximab is conditionally approved in Japan for use in patients with refractory nephrotic syndrome. To meet the conditions of approval, an all-case post-marketing surveillance study was conducted to confirm the real-world safety and efficacy of rituximab in patients of all ages with refractory nephrotic syndrome.MethodsAll patients scheduled to receive rituximab treatment for refractory nephrotic syndrome were eligible to register (registration: August 29, 2014 through April 15, 2016); the planned observation period was 2 years from the initiation of rituximab treatment (intravenous infusion, 375 mg/m2 once weekly for four doses). The study was conducted at 227 hospitals throughout Japan. Adverse drug reactions (ADRs) were collected for safety outcomes. The efficacy outcomes were relapse-free period and the degree of growth in pediatric (< 15 years) patients.ResultsIn total, 997 (447 pediatric) patients were registered; 981 (445) were included in the safety analysis set; 852 (402) completed the 2-year observation period; and 810 (429) were included in the efficacy analysis set. Refractory nephrotic syndrome had developed in childhood for 85.0% of patients, and 54.6% were aged ≥15 years. ADRs were observed in 527 (53.7%) patients, treatment-related infection/infestation in 235 (24.0%) patients, and infusion reactions in 313 (31.9%) patients. The relapse-free period was 580 days (95% confidence interval, 511–664). There was a significant change in height standard deviation score (pediatric patients; mean change, 0.093; standard deviation, 0.637; P = 0.009).ConclusionThe safety and efficacy of rituximab treatment in patients with refractory nephrotic syndrome were confirmed in the real-world setting.Clinical trial registrationUMIN000014997.

POS-455 RITUXIMAB IN MANAGEMENT OF PEDIATRIC NEPHROTIC SYNDROME

Idiopathic nephrotic syndrome is the most common chronic glomerular disease in children. At least 20 % of children with this syndrome show frequent relapses and/or steroid dependence during or after immunosuppressive therapies, a condition defined as complicated frequently relapsing/steroid-dependent nephrotic syndrome (FRNS/SDNS). Approximately 1–3 % of children with idiopathic nephrotic syndrome are resistant to steroids and all immunosuppressive agents, a condition defined as refractory steroid-resistant nephrotic syndrome (SRNS); these SRNS children have a high risk of end-stage renal failure. Many studies in the past decade have reported the effectiveness of rituximab for complicated FRNS/SDNS and refractory SRNS. Prospective study 1) To evaluate the efficacy of rituximab in glomerular diseases. 2) To evaluate response of rituximab by complete or partial remission of nephrotic syndrome after two to four doses of rituximab 375mg/m2, during the follow up period of 12 months and the outcome had been assessed using blood and urine biochemistry values (UPCR/24hr urine protein,serum albumin) i.e., Complete remission (UPCR < 0.2), Partial remission (> 50% decrease in proteinuria from base line), CD 19 cells (< 5%) 3)To look for safety of rituximab. The patients included in the study will be given the dosage of rituximab as per body surface area (BSA) i.e., 375 mg/m2 two to four doses and followed up for a period of 12 months.REGIMEN: 375 mg/m2 Rituximab (2 doses for SDNS, 4 doses for SRNS) after premedication. Inclusion criteria: Patients of age groups <18 yrs were included in the study. Patients with nephrotic syndrome who had received a trial of steroids, alkylating agent and at least 6 months therapy of calcineurin inhibitor had received the novel drug Rituximab. Exclusion criteria: Patients with active focus of infection (Acute/Chronic). Serological evidence of current or past HIV/Hepatitis B/Hepatitis C infection. Known allergic reaction to rituximab. Patients/Parents not willing to give informed consent. Out of 33 patients who received rituximab 18 patients were in SRNS group and 11 were SDNS. The mean age of the patients who used rituximab in SDNS was 13.7+- 9.1 and in SRNS was 10.7+-2.9. In SDNS, FSGS contributed 61% (n=11); MCD33% (n=3) while in SDNS, MCD 72% (n=8); FSGS 27% (n=3). The mean duration of the CNI therapy for SRNS was 20.7=-17.1 months while for SDNS was 18.7+-10.2 months. In SRNS group; Complete remission (CR) was seen in 50.0% while in FSGS 18.1%; partial remission (PR) attained in 33.3% in MCD and in FSGS 27.2% and no remission for 16.6% in MCD and 54.4% in FSGS. In SDNS group, CR was seen in 75.0% in MCD and 33.3% in FSGS; PR obtained in 12.5% in MCD and 66.6% in FSGS; no remission in 12.5% in MCD.The CD19 counts at baseline were 12.6 ± 3.4% of the leukocyte count. After rituximab therapy, CD19 levels were 0.2 ± 0.1 and 0.3 ± 0.2% after two and four doses in patients with SDNS and SRNS, respectively. This study confirm the efficacy of rituximab in patients with difficult nephrotic syndrome; remission was achieved in 50.0% patients with SRNS and a 72.72% patients achieved remission in patients with SDNS. There was a trend toward better response rates in patients with steroid-resistant MCD (83.3%) compared with FSGS (45.45%).

Efficacy of Rituximab in Patients with Autoimmune Bullous Disease: A Retrospective Cohort Study

Efficacy of Rituximab in Patients with Autoimmune Bullous Disease: A Retrospective Cohort Study

The efficacy of rituximab in patients with mucous membrane pemphigoid

Objective Mucous membrane pemphigoid (MMP) is an autoimmune blistering disorder with tendency to scarring. Long term immunosuppressive treatment may be required to minimize the consequences of the disease. Methods In this retrospective study, we investigated the efficacy of rituximab (RTX) in MMP patients and compare the beneficial effects of early versus late administration of RTX. Medical records of 24 MMP patients who were treated with 500 mg RTX on day 1, then weekly for 4 consecutive weeks were reviewed. Results Twenty-one patients (87.5%) reached disease control (DC) at the mean interval of 4.95 months (SD: 5.15; range: 1–24) after RTX. Complete remission (CR) with scarring was achieved in 45.8% (n = 11) and 33.3% (n = 8) attained CR without any residual scar (total CR with or without scar 79.1%). Two patients (8.3%) reached partial remission including persistent gingivitis. Only one patient progressed from non-cicatricial to cicatricial MMP despite receiving RTX. 47.6% (n = 10) of patients experienced relapse after achieving DC at a mean interval of 15.2 months (range: 6–30, SD: 7.0). Considerably, earlier the RTX was administered, sooner the DC was obtained (Pearson r = 0.742, p-value < .001). Conclusions These results suggest that RTX may prevent further scarring and progression in MMP patients especially if administered early.

New Aspects of Pathogenesis and Treatment of Membranous Glomerulopathy After the MENTOR Study

Membranous nephropathy (MN) is the major cause of nephrotic syndrome in adults, accounting for 20% of cases with an annual incidence of 1 per 100,000 population. In the past 10 years, the role of podocytes has been identified. Environmental triggers in genetically predisposed patients can activate podocytes to exhibit antigenic epitopes, including PLA2R, THBS1, and NELL1, which become targets of specific autoantibodies with subsequent complement activation. The discovery of these mechanisms has opened a new horizon in the treatment of MN, and novel drugs are available with more specific mechanisms of action. Rituximab, a monoclonal antibody directed against CD20 expressed on B lymphocytes, has been used in several trials and appears to induce remission of nephrotic syndrome in 60% of patients (GEMRITUX trial). The recently published results of the MENTOR trial documented the superior efficacy of rituximab in patients observed for up to 24 months. In MN, the concept of targeting disease control has introduced novel therapies with specific blocking mechanisms, such as belimumab; nonspecific blocking mechanisms, such as those against adrenocorticotropic hormone; and new therapeutic options, such as ofatumumab, bortezomib, and eculizumab, which have recognised the pathological processes involved in the glomerular diseases.

Effect of rituximab on disease activity in latin American patients with anti-aquaporin-4 (+) neuromyelitis optica spectrum disorder

ObjectivesThe aim of the present study is to explore the efficacy of rituximab in patients with Neuromyelitis Optica spectrum disorders (NMOsd) with positive AQP4-IgG serostatus. Patients and MethodsIn this single center retrospective study, we recruited seropositive anti-AQP4 NMOsd patients who received treatment with Rituximab (RTX) for at least 2 years. Demographics were described and annualized relapse rate (AAR) and survival analysis were performed for time to relapse with Rituximab. All p values ≤0.05 we considered statistically significant. ResultsA total of 15 patients (100 % female) were identified. Mean age of disease onset was 34 ± 11 years, mean time of disease was 8.11 ± 4.04 years and the median number of relapses was 5 (2−16). Ten patients received an immunosuppressive agent before RTX. Mean age of RTX initiation was 37 ± 12 with a mean treatment duration of 52 ± 28 months. The median ARR before and after treatment with RTX was 2.08 vs 0.00, respectively, with a difference of −2.08 (p < 0.001) ConclusionsThis study shows a statistically significant reduction in the ARR and an increase in the relapse-free rate in AQP4-IgG NMOsd patients treated with RTX. These findings support the use of rituximab in our population, and indirectly suggests that its prompt use could modify the course of the disease.

Efficacy of rituximab in patients with Graves' orbitopathy: a retrospective multicenter nationwide study.

The clinical utility of rituximab (RTX) in Graves' orbitopathy (GO) treatment remains controversial since the discrepant results from 2 prospective randomized studies (Stan M et al. J Clin Endocrinol Metab 2015; Salvi M et al. J Clin Endocrinol Metab 2015). The aim of this study was to assess in real life the characteristics and the clinical outcomes of patients with GO treated with RTX in cases of corticosteroid resistance or corticosteroid dependence. Multicenter French retrospective study including patients with moderate-to-severe GO requiring second-line treatment with RTX. Patients were classified according to three main baseline characteristics: clinical inflammation (CAS ≥ 3), oculomotor limitation, and visual dysfunction. Patients were considered as responders if, at 24weeks (week 24), at least 1 of these 3 parameters improved with no worsening elsewhere. Forty patients were included (65% smokers, 38% dysthyroidism). Thirty-two patients were treated with RTX alone (one patient excluded owing to side effects): 64.5% had favorable responses at week 24 and significant reduction in baseline CAS (3.29 ± 1.6) at 12weeks (1.93 ± 1.1; P < 0.001) and at week 24 (1.59 ± 1.1; P < 0.001); reduction in anti-TSH receptor antibodies at week 24 (P < 0.01); and significant improvement of visual acuity (P = 0.04) and ocular hypertonia (P = 0.04) at week 12, but no improvement in oculomotor dysfunction. Eight patients needed emergency treatment with concomitant RTX and orbital decompression, with favorable outcome for 5 patients. Predictive factors for a poor response to RTX were low baseline CAS, smoker, and baseline ocular hypertonia. All patients reported good tolerance except one serious side effect (a cytokine release syndrome). The efficiency results of RTX in reducing CAS in this cohort are just between those of Stan and Salvi. This could be explained by our delay before treatment initiation, quicker than Stan but longer than Salvi. RTX appears to be effective as a second-line treatment for the inflammatory component of GO, especially if the disease is highly active and recent.

Efficacy of rituximab in difficult-to-manage autoimmune hepatitis: Results from the International Autoimmune Hepatitis Group.

Background & AimsTreatment options remain limited for patients with autoimmune hepatitis (AIH), while there are still concerns over the consequences of long-term corticosteroid use. A few studies have suggested a role for B cell-driven autoimmune liver injury in AIH. This multicentre, international retrospective cohort study from the International Autoimmune Hepatitis Group aims to evaluate the clinical efficacy and safety of rituximab in difficult-to-manage AIH.MethodsClinical data from 22 patients who received rituximab between 2007 and 2017 were collected from centres in the United Kingdom, Germany and Canada. Clinical response was assessed using changes in biochemical and immunological parameters up to 24 months post-rituximab infusion. In addition, we compared the doses of prednisolone used 3 months before and 12 months after treatment, and assessed freedom from AIH flares over the post-treatment period.ResultsTwenty-two patients with type-1 AIH were included, with a median age of 40 years at diagnosis (range 19–79); 15/22 (68%) were female and 18/22 (82%) were Caucasian. The median period from diagnosis to the end of follow-up in these patients was 11 years (range 3–28). Values of alanine aminotransferase, aspartate aminotransferase and albumin improved significantly following rituximab therapy, and were sustained for up to 2 years (all p ≪0.001). Prednisolone doses were significantly reduced by 12 months post-treatment (p = 0.003), with 13/21 (62%) patients having a dose reduction. Over a median post-treatment follow-up period of 6 years (range 1–10), 5 patients developed AIH flares at a median of 22 months post-treatment, giving an estimated 71% freedom from AIH flare at 2 years. Four of these patients received a second course of treatment, of whom 2 had subsequent further flares. No serious adverse events attributable to rituximab were recorded.ConclusionIn patients with difficult-to-manage AIH, rituximab appears to be clinically effective and well tolerated. Rituximab was associated with sustained improvements in serum liver tests, an absence of clinical disease flares, and a reduction in prednisolone dose. Controlled trials are warranted to further evaluate B cell-targeting therapies in patients with AIH.Lay summaryAutoimmune hepatitis is an autoimmune condition of the liver, usually treated with medications that suppress the immune system, such as steroids. However, some patients do not respond to this treatment. We analysed the safety and efficacy of rituximab in patients who were not responding to first- or second-line therapies. Rituximab was safe and improved liver blood tests in 70% of patients over a 2-year follow-up period, while enabling steroid doses to be reduced in two-thirds of patients, which is a very positive clinical outcome.

Efficacy and safety of rituximab in systemic sclerosis: French retrospective study and literature review.

To describe safety and efficacy of rituximab in patients with systemic sclerosis. We included 13 patients with systemic sclerosis treated with rituximab and pooled with 40 additional patients from the literature. SSc rituximab untreated patients were matched to rituximab treated ones. Thirteen patients who received rituximab and 26 rituximab-untreated patients were included. In comparison to 26 patients who did not received rituximab, FVC changes were not significantly different, whereas DLCO improved in 13 patients who received rituximab (0 [-4; 4] vs loss of -7 [-19; 0]; p=0.05). Considering 7 rituximab treated and 14 untreated diffuse SSc, FVC was improved during the 24 [12; 46] months of follow up in dSSc who received rituximab (gain of 12 [7.5:14] % vs loss of 1.5 [-16.8; 2.5], (p=0.003)). Pooled analysis of 53 patients (40 literature patients and 13 from personal series) showed significant improvement of median mRSS from 18 [8; 32] at baseline to 9 [4; 18] at M6 (p=0.007), 13 [8; 18] at M12 (p=0.008) and 10 [4; 16] at the last follow-up (p=0.0002). FVC increased from 71% [66; 80] at baseline to 84% [75; 90] at M12 (p=0.001). DLCO increased from 58% [39; 65] at M0 to 63% [53; 78] at M12 (p=0.04). Our personal data and pooled literature analysis suggest the efficacy of rituximab in the subset of diffuse SSc in particular in skin and interstitial disease involvements. The safety of rituximab seems to be reasonable and similar to previous data in other autoimmune diseases.